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Blood Monocytes (blood + monocyte)
Kinds of Blood Monocytes Selected AbstractsHepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis,HEPATOLOGY, Issue 1 2009Karlin Raja Karlmark In addition to liver-resident Kupffer cells, infiltrating immune cells have recently been linked to the development of liver fibrosis. Blood monocytes are circulating precursors of tissue macrophages and can be divided into two functionally distinct subpopulations in mice: Gr1hi (Ly6Chi) and Gr1lo (Ly6Clo) monocytes. The role of these monocyte subsets in hepatic fibrosis and the mechanisms of their differential recruitment into the injured liver are unknown. We therefore characterized subpopulations of infiltrating monocytes in acute and chronic carbon tetrachloride (CCl4)-induced liver injury in mice using flow cytometry and immunohistochemistry. Inflammatory Gr1hi but not Gr1lo monocytes are massively recruited into the liver upon toxic injury constituting an up to 10-fold increase in CD11b+F4/80+ intrahepatic macrophages. Comparing wild-type with C-C chemokine receptor (CCR2)-deficient and CCR2/CCR6,deficient mice revealed that CCR2 critically controls intrahepatic Gr1hi monocyte accumulation by mediating their egress from bone marrow. During chronic liver damage, intrahepatic CD11b+F4/80+Gr1+ monocyte-derived cells differentiate preferentially into inducible nitric oxide synthase,producing macrophages exerting proinflammatory and profibrogenic actions, such as promoting hepatic stellate cell (HSC) activation, T helper 1,T cell differentiation and transforming growth factor , (TGF-,) release. Impaired monocyte subset recruitment in Ccr2,/, and Ccr2,/,Ccr6,/, mice results in reduced HSC activation and diminished liver fibrosis. Moreover, adoptively transferred Gr1hi monocytes traffic into the injured liver and promote fibrosis progression in wild-type and Ccr2,/,Ccr6,/, mice, which are otherwise protected from hepatic fibrosis. Intrahepatic CD11b+F4/80+Gr1+ monocyte-derived macrophages purified from CCl4 -treated animals, but not naïve bone marrow monocytes or control lymphocytes, directly activate HSCs in a TGF-,,dependent manner in vitro. Conclusion: Inflammatory Gr1+ monocytes, recruited into the injured liver via CCR2-dependent bone marrow egress, promote the progression of liver fibrosis. Thus, they may represent an interesting novel target for antifibrotic strategies. (HEPATOLOGY 2009;50:261,274.) [source] Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1,JOURNAL OF MEDICAL VIROLOGY, Issue 11 2007Hamid Hasson Abstract In multidrug resistant patients treatment interruptions allow the selection of archived wild-type drug-susceptible viruses that compete for the less fit drug-resistant strains. However, the selection of viruses with increased replicative capacity is often followed by a loss of CD4+ T cells. In addition, drug resistant variants later re-emerge limiting the overall clinical benefit of treatment interruption. Blood monocytes are a key component of the HIV reservoir and can be partially removed by a system for purging of myeloid cells (MYP). This study tested the safety and efficacy of MYP on multidrug resistant patients who underwent treatment interruption. Twelve patients were randomized to receive or not six cycles of MYP during treatment interruption. An optimized antiretroviral regimen was reintroduced after the reappearance of a drug susceptible genotype. Following therapy reintroduction, a long lasting increase in CD4+ T cell counts was observed only in the treatment interruption,+,MYP patients but not in the control patients. Five/six treatment interruption,+,MYP patients never experienced virological rebound during a median follow up period of 98 weeks. In contrast, 4/6 patients who did not receive MYP never reached complete viral suppression and had a virological rebound after a median of 16.5 weeks after treatment reintroduction. The difference between the two groups in the time to virological rebound was statistically significant (P,=,0.021). A consistent decrease of HIV DNA load in CD14+ purified cells was observed only in treatment interruption,+,MYP patients. These data suggest that MYP can improve the immunological and virological response to treatment interruption. J. Med. Virol. 79:1640,1649, 2007. © 2007 Wiley-Liss, Inc. [source] Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levelsCYTOMETRY, Issue 1 2005Bruce H. Davis Abstract Background CD163 is a monocyte/macrophage-restricted receptor involved in the clearance of hemoglobin,haptoglobin complexes and regulation of inflammatory processes. CD163 is shed from the cell surface and exists as a soluble form in plasma (sCD163). Monocyte CD163 and sCD163 are potential diagnostic tools in variety of disease states. Methods We determined the relation between plasma sCD163 levels by enzyme-linked immunosorbent assay, membrane expressions of CD163, CD64, and CD14 on blood monocytes by flow cytometry, and monocyte counts in 129 random blood samples. Results A strong inverse correlation was found between membrane CD163 expression and sCD163 levels (r = ,0.65, P < 0.001). Monocyte CD163 expression and SCD163 levels did not correlate with the monocyte absolute count. Conclusions The inverse relation between monocyte surface CD163 expression and sCD163 levels in human blood suggests that plasma sCD163 is derived from circulating monocytes, in addition to an unknown component from tissue macrophages. The lack of correlation with the absolute monocyte number suggests that such a balance is driven by the functional state of monocytes, rather than simply by numerical changes in circulating cells. We propose that further clinical evaluations of CD163 as a diagnostic parameter should include simultaneous measurements of soluble and cell-bound forms of this antigen. © 2004 Wiley-Liss, Inc. [source] Targeted replacement of rodent CCR2 with the human orthologue CCR2B: A mouse model for in vivo analysis of human target-selective small molecule MCP-1 receptor antagonistsDRUG DEVELOPMENT RESEARCH, Issue 4 2002Haydn M. Prosser Abstract Rodent models for testing the efficacy of lead compounds are often invalidated by species selectivity of the compounds. The advent of mouse embryonic stem cell technology has allowed the development of genetically engineered mouse strains that incorporate a specific human gene in place of the orthologous mouse gene, a so-called knock-in mouse. This study describes the generation and validation of a mutant mouse line that expresses human CCR2B as a functional substitute for murine CCR2. The human CCR2B knock-in mice are viable and appear normal. In vitro assays indicate that the CCR2B knock-in is functionally expressed, giving a macrophage chemotactic profile in response to JE or MCP-1 that is similar to human peripheral blood monocytes rather than that of a murine macrophage cell line. In addition, the human selective CCR2B antagonist, SB-399721, was a more potent inhibitor of CCR2B knock-in macrophages in response to hMCP-1 than JE. The ability of the human CCR2B gene to functionally substitute for the mouse orthologue in vivo is demonstrated by a normal inflammatory response to intraperitoneal thioglycollate injection. Drug Dev. Res. 55:197,209, 2002. © 2002 Wiley-Liss, Inc. [source] Interactions between major histocompatibility complex class II surface expression and HIV: implications for pathogenesisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2001W. Kamp Although it has been almost 20 years since the first cases of acquired immunodeficiency syndrome (AIDS) were documented, the pathogenesis is still not completely understood. Interactions between major histocompatibility complex (MHC) Class I and human immunodeficiency virus (HIV), resulting in down-regulation of MHC-I surface expression, have been reported to contribute to pathogenesis by suppressing the host's immune response. Interactions between MHC Class II and HIV have also been described, but it is unclear how these contribute to the pathogenesis. MHC-II surface expression on HIV-infected monocytes and monocytic cell lines has been described to be increased as well as decreased when compared to uninfected control monocytes. HIV-specific mechanisms appear to down-regulate MHC-II expression on blood monocytes during HIV-1 infection, whereas host mechanisms up-regulate MHC-II expression in response to infection of blood monocytes as well as brain macrophages. A balance between these two may determine MHC-II expression levels in individual patients. Altogether, HIV seems to be able to benefit from both low and high levels of MHC-II surface expression. The first results in reduced immune surveillance of the host, allowing the virus to replicate faster; the second increases infectivity of the virus as a result of higher MHC-II density on macrophages and virion particles. [source] Differential expression of mast cell characteristics in human myeloid cell linesEXPERIMENTAL DERMATOLOGY, Issue 9 2004Pia Welker Abstract:, In order to better understand the mechanisms governing display of mast cell characteristics in human myeloid cells, we have studied the mast cell phenotype in human promyelocytic (HL-60) and myelocytic (U-937, TPH-1) vs. basophilic (KU-812) and mast cell (HMC-1) lines, in part also in skin mast cells and blood monocytes, at mRNA and protein level before and after stimulation with mast cell growth factors. In unstimulated cells, mRNA for the stem cell factor (SCF) receptor c-kit and the gamma chain of the high-affinity IgE receptor (Fc,RI) was noted in all cells studied. Like mast and basophilic cells, THP-1 cells expressed the Fc,RI, and , chains and weakly histidine decarboxylase (HDC), but they lacked mRNA for mast cell-specific proteases [tryptase, chymase, carboxypeptidase A (CPA)]. In contrast, HL-60 and U-937 cells lacked Fc,RI,, but expressed tryptase and chymase, HL-60 cells also CPA. KU-812 cells failed to express the basophil-specific marker 2D7. After a 10-day culture with SCF or fibroblast supernatants, baseline mRNA expression of most mast cell characteristics was upregulated, whereas c-kit mRNA expression decreased in all but THP-1 cells. Differential mRNA expression of Fc,RI vs. protease (tryptase) was confirmed at protein level by immunocytochemistry and enzymatic activity. KU-812 cells are thus closest to skin mast cells in that they express all molecules studied, except for chymase, followed by THP-1 cells that lack all mast cell proteases. In contrast, HL-60 and U-937 cells fail to express the Fc,RI, and , chains but express most mast cell proteases. The selective and differential expression of mast cell characteristics in human myeloid cell lines suggests that induction of the mast cell phenotype is regulated by several independent genes and that mast cells and basophils branch off at early and distinct points of myeloid development. [source] TNF-, suppresses dendritic cell death and the production of reactive oxygen intermediates induced by plasma withdrawalEXPERIMENTAL DERMATOLOGY, Issue 5 2004Hong-Duck Um Abstract:, Mature dendritic cells (DCs) were generated by culturing human peripheral blood monocytes for 7 days and, then, treating them with a cytokine cocktail for 2 days. The viability of the mature DCs (Day 9) obtained was approximately 60,70%, and this gradually declined when they were recultured in X-VIVO 15 media containing 2% human plasma (40% viability after 3 days of reculture). DC death accelerated on withdrawing plasma from the culture (20% viability after 3 days). However, the addition of tumor necrosis factor-, (TNF-,) to the medium completely restored DC viability in the absence of plasma. Such a protective effect was not afforded by other cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1, (IL-1,), IL-4, IL-6 and prostaglandin E2 which are used for the maturation of DCs. These results indicate that TNF-, is specifically required to maintain the viability of mature DCs. The withdrawal of plasma rapidly (within 15 min) elevated cellular levels of reactive oxygen intermediates (ROIs), which have been proposed to regulate the ability of DCs to control inflammatory reactions. The possibility that ROIs act as mediators of DC death was eliminated by the observation that scavengers of ROIs, such as catalase, N -acetylcysteine, glutathione, failed to prolong DC life span in the absence of plasma. Interestingly, TNF-, was found to almost completely abolish the production of ROIs induced by plasma withdrawal. To summarize, our results suggest that TNF-, controls not only the inflammatory functions of DCs but also their survival. [source] Rat choroid plexuses contain myeloid progenitors capable of differentiation toward macrophage or dendritic cell phenotypesGLIA, Issue 3 2006Serge Nataf Abstract The interface between the blood and the cerebrospinal fluid (CSF) is formed by the choroid plexuses (CPs), which are specialized structures located within the brain ventricles. They are composed of a vascularized stroma surrounded by a tight epithelium that controls molecular and cellular traffic between the blood and the CSF. Cells expressing myeloid markers are present within the choroidal stroma. However, the exact identity, maturation state, and functions of these CP-associated myeloid cells are not fully clarified. We show here that this cell population contains immature myeloid progenitors displaying a high proliferative potential. Thus, in neonate rats and, to a lesser extent, in adult rats, cultured CP stroma cells form large colonies of macrophages, in response to M-CSF or GM-CSF, while, under the same conditions, peripheral blood monocytes do not. In addition, under GM-CSF treatment, free-floating colonies of CD11c+ monocytic cells are generated which, when restimulated with GM-CSF and IL-4, differentiate into OX62+/MHC class II+ dendritic cells. Interestingly, in CP stroma cultures, myeloid cells are found in close association with fibroblastic-like cells expressing the neural stem-cell marker nestin. Similarly, in the developing brain, macrophages and nestin+ fibroblastic cells accumulate in vivo within the choroidal stroma. Taken together, these results suggest that the CP stroma represents a niche for myeloid progenitors and may serve as a reservoir for brain macrophages. © 2006 Wiley-Liss, Inc. [source] Interleukin-6 Induction by Helicobacter pylori in Human Macrophages is Dependent on PhagocytosisHELICOBACTER, Issue 3 2006Stefan Odenbreit Abstract Background:, The colonization of the gastric mucosa with Helicobacter pylori is accompanied by elevated levels of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and IL-8. The aim of our study was to determine the mechanisms of IL-6 stimulation in phagocytes upon H. pylori infection. Materials and Methods:, We investigated the secretion of IL-6 by different professional phagocytes from murine and human origin, including granulocyte- and monocyte-like cells and macrophages derived from human peripheral blood monocytes (PBMCs). The influence of viability, phagocytosis, and the impact of different subcellular fractions of H. pylori bacteria were evaluated. Results:, IL-6 levels induced by H. pylori were low in cell lines derived from murine and human monocytes and in human granulocyte-like cells. By contrast, macrophages derived from human PBMCs were highly responsive to both H. pylori and Escherichia coli. IL-6 induction was blocked by inhibition of actin-dependent processes prior to infection with H. pylori, but not with E. coli or E. coli lipopolysaccharide (LPS). Using cell fractionation, the most activity was found in the H. pylori membrane. H. pylori LPS exhibited a 103 - to 104 -fold lower biologic activity than E. coli LPS, suggesting a minor role for toll-like receptor 4 (TLR4)-mediated signalling from the exterior. Conclusions:, From these data, we conclude that macrophages may be a major source of IL-6 in the gastric mucosa upon H. pylori infection. The IL-6 induction by H. pylori in these cells is a multifactorial process, which requires the uptake and presumably degradation of H. pylori bacteria. [source] Protein array technology to investigate cytokine production by monocytes from patients with advanced alcoholic cirrhosis: An ex vivo pilot studyHEPATOLOGY RESEARCH, Issue 7 2009Khalid A. Tazi Aim:, In patients with advanced cirrhosis, little is known about the ability of peripheral blood monocytes to spontaneously produce signaling proteins such as cytokines. The aim of this ex vivo study was to evaluate cytokine production under baseline conditions and after stimulation by lipopolysaccharide (LPS), a toll-like receptor (TLR) agonist. Methods:, Peripheral blood monocytes were isolated from patients with advanced alcoholic cirrhosis (without ongoing bacterial infections) and normal subjects. Cells were left unstimulated or were stimulated with LPS. The abundance of 24 cytokines was measured using a filter-based, arrayed sandwich enzyme-linked immunosorbent assay (ELISA) in the supernatant of cultured monocytes. Results:, Cirrhotic monocytes spontaneously produced six proteins (TNF-,, IL-6, IL-8, MCP-1, RANTES and Gro), whereas normal monocytes produced only small amounts of IL-8 and RANTES. Analyses with the online gene set analysis toolkit WebGestalt (http://bioinfo.vanderbilt.edu/webgestalt) found enrichment for the six proteins in the human gene ontology subcategory (http://www.geneontology.org), Kyoto Encyclopedia of Genes and Genome pathways (http://www.genome.ad.jp/kegg/) and BioCarta pathways (http://www.biocarta.com/genes/index.asp) consistent with a proinflammatory phenotype of cirrhotic monocytes resulting from activated TLR signaling. Interestingly, LPS-elicited TLR engagement further increased the production of the six proteins and did not induce the secretion of any others, in particular the anti-inflammatory cytokine IL-10. LPS-stimulated normal monocytes produced TNF-,, IL-6, IL-8, MCP-1, RANTES, Gro and IL-10. Conclusion:, In patients with advanced cirrhosis, peripheral blood monocytes spontaneously produce proinflammatory cytokines, presumably in response to unrestricted TLR signaling. [source] Serum lipids regulate dendritic cell CD1 expression and functionIMMUNOLOGY, Issue 3 2008David S. Leslie Summary Dendritic cells (DCs) are highly potent antigen-presenting cells (APCs) and play a vital role in stimulating naïve T cells. Treatment of human blood monocytes with the cytokines granulocyte,macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 stimulates them to develop into immature dendritic cells (iDCs) in vitro. DCs generated by this pathway have a high capacity to prime and activate resting T cells and prominently express CD1 antigen-presenting molecules on the cell surface. The presence of human serum during the differentiation of iDCs from monocytes inhibits the expression of CD1a, CD1b and CD1c, but not CD1d. Correspondingly, T cells that are restricted by CD1c showed poor responses to DCs that were generated in the presence of human serum, while the responses of CD1d-restricted T cells were enhanced. We chemically fractionated human serum to isolate the bioactive factors that modulate surface expression of CD1 proteins during monocyte to DC differentiation. The human serum components that affected CD1 expression partitioned with polar organic soluble fractions. Lysophosphatidic acid and cardiolipin were identified as lipids present in normal human serum that potently modulate CD1 expression. Control of CD1 expression was mediated at the level of gene transcription and correlated with activation of the peroxisome proliferator-activated receptor (PPAR) nuclear hormone receptors. These findings indicate that the ability of human DCs to present lipid antigens to T cells through expression of CD1 molecules is sensitively regulated by lysophosphatidic acid and cardiolipin in serum, which are ligands that can activate PPAR transcription factors. [source] Expression of ,-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cellsIMMUNOLOGY, Issue 4 2002Louise A. Duits Summary Human ,-defensins are broad-spectrum antimicrobial peptides known to be produced by epithelial cells. It was recently shown that ,-defensins also display chemotactic activity for dendritic cells (DC) and T cells, and thus may serve to link innate and adaptive immunity. The aim of the present study was to explore expression of mRNA for these peptides in mononuclear phagocytes and DC. The results revealed that monocytes, monocyte-derived-macrophages (MDM), and monocyte-derived-dendritic cells (DC) all express human-,-defensin-1 (hBD-1) mRNA. hBD-1 mRNA expression by monocytes and MDM was increased after activation with interferon-, (IFN-,) and/or lipopolysaccharide (LPS) in a dose- and time-dependent fashion. Alveolar macrophages showed an intense hBD-1 expression, which could not be further increased. Expression of hBD-1 mRNA by immature DC was low, and increased considerably after maturation. Monocytes, MDM, alveolar macrophages and DC showed a limited expression of human ,-defensin-2 (hBD-2) mRNA, which could only be increased in monocytes and alveolar macrophages by IFN-, and/or LPS in a dose- and time-dependent fashion. Immunocytochemical stainings demonstrated the expression of hBD-2 peptide by freshly isolated blood monocytes and alveolar macrophages in cytospin preparations. [source] NOD2/CARD15 genotype influences MDP-induced cytokine release and basal IL-12p40 levels in primary isolated peripheral blood monocytesINFLAMMATORY BOWEL DISEASES, Issue 8 2008Vanessa Beynon MD Abstract Background: The functional link between mutations in NOD2 and Crohn's disease (CD) has not been entirely elucidated. The 1007fs mutation results in loss of NF-,B activation in response to muramyl dipeptide (MDP) but has also been linked to an increased IL-1, processing and IL-12 release. Methods: We investigated the basal and MDP-triggered mRNA expression and protein release for TNF-,, IL-10, IL-1,, and IL-12p40 in peripheral blood monocytes from 40 CD patients and 15 healthy individuals with different NOD2 genotypes. Results: Monocytes from individuals with 2 mutated NOD2 alleles (homozygous and compound-heterozygous individuals) displayed an impaired release of TNF-, and IL-10 but also of IL-1, and IL-12p40 in response to MDP. In contrast to other NOD2 variants, the presence of at least 1 1007fs allele in double-mutated individuals completely abrogated NOD2 receptor function. Interestingly, monocytes from CD patients with 2 mutated NOD2 alleles displayed significantly higher basal levels of IL-12p40 in cell culture supernatants compared to wildtype CD patients and control individuals (P = 0.002 and P = 0.008, respectively). This was regardless of the IL23R genotype and was not mirrored by increased IL-12p40 plasma levels in these individuals. Conclusions: The CD-associated NOD2 variants lead, in a dose- and mutation-dependent manner, to an impaired release of TNF-,, IL-10, IL-1,, and IL-12p40 in response to MDP. The finding of increased basal levels for IL-12p40-related cytokines in monocytes with 2 mutated NOD2 alleles is likely to set a new link between NOD2 mutations and the inflammatory mechanisms underlying CD. (Inflamm Bowel Dis 2008) [source] Cytotoxic T lymphocyte mediated recognition of human pancreatic cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2002Matthias Peiper Abstract T lymphocytes play an important role in tumor rejection and their response to human malignant melanoma has been well documented. In contrast, the existence of cytotoxic T lymphocytes (CTL) to pancreatic cancer remains unclear. Tumor-associated lymphocytes (TAL) and peripheral blood monocytes (PBMC) were isolated from pancreatic cancer patients. Tumor-specific CTL were generated from TAL and PBMC using solid-phase anti-CD3, low-dose IL-2 (50 IU/ml) and repetitive autologous tumor stimulation. The specificity of CTL was tested in standard cytotoxicity assays using autologous tumor cells, autologous fibroblasts when available, several allogeneic pancreatic tumor cells and the NK-sensitive cell line K562. Anti-HLA-Class I MAb, W6/32, was used to demonstrate that tumor-specific CTL were HLA-Class I restricted. HLA-molecules of human pancreatic cancer cells were washed out using acid elution. Eight consecutive, histologically confirmed pancreatic cancer specimen as well as peripheral blood mononuclear cells were analyzed. CTL were capable of lysing autologous tumor cells significantly after 3 stimulations with autologous tumor cells. T cell mediated recognition was HLA-Class I restricted as shown by incubation with MAb anti-HLA-Class I. In case of HLA-A2 positivity, incubation of tumor cells in cytotoxicity assays resulted in significant inhibition. Autologous fibroblasts or K562 cells were lysed significantly less. HLA-Class I molecule elution resulted in significantly lower recognition of these cells by CTL. These results show for the first time in a larger series the possibility of generating CTL in human pancreatic cancer. The identification of new tumor associated antigens or tumor antigens will be crucial for establishing new treatment strategies. © 2002 Wiley-Liss, Inc. [source] Tissue granuloma structure-function in experimental visceral leishmaniasisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2001Henry W. Murray In experimental visceral leishmaniasis in normal mice (BALB/c, C57BL/6) acquired resistance to Leishmania donovani, a protozoan which targets tissue macrophages, depends upon T cells, Th1 cell-type cytokine generation and activated mononuclear phagocytes. In the intact host, initial control and eventual resolution of L. donovani hepatic infection in normal mice is expressed by and accomplished within well-formed, mature tissue granulomas. In the liver, these immunologically active, inflammatory structures are assembled around a core of fused, parasitized resident macrophages (Kupffer cells) which come to be encircled by both cytokine-secreting T cells and influxing leishmanicidal blood monocytes. This pro-host defense granuloma structure-function relationship, in which histologically mature granulomas provide the microenvironment for intracellular L. donovani killing, however, is only one of seven which have been identified through experimental modifications in this model. This report reviews these structure-function relationships and illustrates the broad spectrum of additional possible responses. These responses range from structurally intact granulomas which provide no antileishmanial function (the ,ineffective' granuloma), to enlarged granulomas which show enhanced parasite killing (the ,hypertrophied' granuloma), to effective antileishmanial activity in the absence of any tissue reaction (the ,invisible' granuloma). [source] Periodontal therapy alters gene expression of peripheral blood monocytesJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2007Panos N. Papapanou Abstract Aims: We investigated the effects of periodontal therapy on gene expression of peripheral blood monocytes. Methods: Fifteen patients with periodontitis gave blood samples at four time points: 1 week before periodontal treatment (#1), at treatment initiation (baseline, #2), 6-week (#3) and 10-week post-baseline (#4). At baseline and 10 weeks, periodontal status was recorded and subgingival plaque samples were obtained. Periodontal therapy (periodontal surgery and extractions without adjunctive antibiotics) was completed within 6 weeks. At each time point, serum concentrations of 19 biomarkers were determined. Peripheral blood monocytes were purified, RNA was extracted, reverse-transcribed, labelled and hybridized with AffymetrixU133Plus2.0 chips. Expression profiles were analysed using linear random-effects models. Further analysis of gene ontology terms summarized the expression patterns into biologically relevant categories. Differential expression of selected genes was confirmed by real-time reverse transcriptase-polymerase chain reaction in a subset of patients. Results: Treatment resulted in a substantial improvement in clinical periodontal status and reduction in the levels of several periodontal pathogens. Expression profiling over time revealed more than 11,000 probe sets differentially expressed at a false discovery rate of <0.05. Approximately 1/3 of the patients showed substantial changes in expression in genes relevant to innate immunity, apoptosis and cell signalling. Conclusions: The data suggest that periodontal therapy may alter monocytic gene expression in a manner consistent with a systemic anti-inflammatory effect. [source] Long-term effect of full-mouth tooth extraction on the responsiveness of peripheral blood monocytesJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2003Schelte J. Fokkema Abstract Background: As some residual inflammation may remain after periodontal therapy, the present pilot study investigated the long-term effect of full-mouth tooth extraction therapy on the responsiveness of peripheral blood monocytes in a case with generalized terminal adult periodontitis. Methods: Before and 3, 9, 20 and 32 months after therapy, venous blood was collected. Total and differential white blood cell counts were determined and whole blood cell cultures (WBCC) were incubated with lipopolysaccharide (LPS) to stimulate the production of inflammatory mediators by monocytes. Results: After full-mouth tooth extraction, the numbers of total peripheral white blood cells and neutrophils decreased over time. The release of the chemokines interleukin (IL)-8 and macrophage chemoattractant protein (MCP)-1 in the cultures decreased twofold over time, whereas no changes were seen for the other studied cytokines, chemokines and prostaglandin E2. Conclusion: On the basis of previous studies and the present case, the high production of IL-8 and MCP-1 by monocytes in LPS-stimulated WBCC from periodontitis patients is most likely acquired, as their levels decrease over time when the periodontal infection is controlled. The possible connection between periodontitis and atherosclerosis through IL-8 and MCP-1 is discussed. Zusammenfassung Hintergrund: Da nach der parodontalen Therapie eine restliche Entzündung zurückbleiben kann, untersucht die vorliegende Studie den Langzeiteffekt einer vollständigen Zahnextraktion auf die Ansprechbarkeit der peripheren Blutmonozyten in einem Fall mit generalisierter unheilbarer Erwachsenen-Parodontitis. Methoden: Vor und 3, 9, 20 und 32 Monaten nach der Therapie wurde venöses Blut gesammelt. Der totale und differenzierte weiße Blutzellgehalt wurden bestimmt, und eine gesamte Blutzellkultur (WBCC) wurde mit Lipopolysaccharid inkubiert, um die Produktion von Entzündungsmediatoren durch Lymphozyten zu stimulieren. Ergebnisse: Nach der vollständigen Zahnextraktion verringerte sich die Zahl der totalen peripheren weißen Blutzellen und der Neutrophilen über die Zeit. Die Freisetzung des Chemokins Interleukin 8 (IL-8) und des Makrophagen chemoattraktanten Proteins (MCP) ,1 in den Kulturen verringerte sich zweifach über die Zeit, während für die anderen beobachteten Cytokine, Chemokine und Prostaglandin E2 keine Veränderungen festgestellt wurden. Schlussfolgerung: Auf der Basis vorheriger Studien und des vorliegenden Falls ist die hohe Produktion von IL-8 und MCP-1 durch Monozyten in LPS stimulierten WBCC von Parodontitis-Patienten sehr wahrscheinlich anzunehmen, da ihr Level über die Zeit abnimmt, wenn die parodontale Infektion kontrolliert ist. Die mögliche Verbindung zwischen Parodontitis und Arteriosklerose durch IL-8 und MCP-1 wird diskutiert. Résumé Contexte: Puisqu'après traitement parodontal, une inflammation résiduelle peut subsister, cette étude se propose de rechercher les effets à long terme de l'extraction complète des dents sur la réponse des monocytes périphériques dans un cas de parodontite de l'adulte terminale généralisée. Méthodes: Des prélèvements sanguins veineux ont été réalisés avant et 3, 9, 20 et 32 mois après traitement. Les comptages totaux et relatifs des cellules blanches sanguines furent déterminés et les cultures complètes de cellules sanguines (WBCC) furent incubées avec du lipopolysaccharide pour stimuler la production des médiateurs de l'inflammation par les monocytes. Résultats: Après l'extraction complète des dents, les nombres de cellules sanguines blanches totales périphériques et des neutrophiles diminuaient au cours du temps. Le relargage des chimiokines interleukine (IL)-8 et protéine chimio-attractante du macrophage (MCP)-1 dans les cultures diminuait deux fois au cours du temps, alors qu'aucun changement n'était observé pour les autres cytokines étudiées, chimiokines et prostaglandine E2. Conclusion: Sur la base d'études préalables, et les résultats issus de ce cas présent, la forte production d'IL-8 et de MCP-1 par les monocytes dans les WBCC stimulés par le LPS chez des patients atteints de parodontite semble être vraisemblablement acquise puisque leurs niveaux diminuent lorsque l'infection parodontale est contrôlée. La relation possible entre parodontite et l'athérosclérose par IL-8 et MCP-1 est discutée. [source] Chlamydia pneumoniae infection promotes the transmigration of monocytes through human brain endothelial cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2003A. MacIntyre Abstract We have investigated the effects of Chlamydia pneumoniae on human brain endothelial cells (HBMECs) and human monocytes as a mechanism for breaching the blood-brain barrier (BBB) in Alzheimer's disease (AD). HBMECs and peripheral blood monocytes may be key components in controlling the entry of C. pneumoniae into the human brain. Our results indicate that C. pneumoniae infects blood vessels and monocytes in AD brain tissues compared with normal brain tissue. C. pneumoniae infection stimulates transendothelial entry of monocytes through HBMECs. This entry is facilitated by the up-regulation of VCAM-1 and ICAM-1 on HBMECs and a corresponding increase of LFA-1, VLA-4, and MAC-1 on monocytes. C. pneumoniae infection in HBMECs and THP-1 monocytes up-regulates monocyte transmigration threefold in an in vitro brain endothelial monolayer. In this way, C. pneumoniae infection in these cell types may contribute to increased monocyte migration and promote inflammation within the CNS resulting from infection at the level of the vasculature. Thus, infection at the level of the vasculature may be a key initiating factor in the pathogenesis of neurodegenerative diseases such as sporadic AD. © 2002 Wiley-Liss, Inc. [source] Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclast formation of human blood monocytes without cell to cell contactJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2005Makoto Nishimura Abstract When human blood monocytes were cocultured with stromal cells derived from human giant cell tumor of bone (GCTSC) and a Millipore filter (0.4 ,m) was interposed between monocytes and GCTSC, multinucleated giant cell formation of monocytes was induced. The multinucleated giant cells have characters as osteoclast-like cells, indicating that a soluble osteoclast-inducing factor(s) is secreted from GCTSC expressing RANK, RANKL/ODF/OPGL and TACE mRNA. Furthermore, OCIF/OPG inhibited GCTSC-induced osteoclastogenesis, showing that the RANK,RANKL system is involved in GCTSC-induced osteoclastogenesis and that soluble form of ODF/RANKL induces osteoclasts from monocytes. GCTSC expressed the cytokine mRNAs such as M-CSF, GM-CSF, IL-3, IL-4, IL-6, and IFN-, mRNAs. None of IL-1r,, IL-1,, IL-1,, IL-2, IL-4, IL-10, IL-18, TNF-,, GCSF and IFN-, could be detected in all culture media. A significant amount of IL-6 could be detected in the culture media of all GCTSC. IL-8 was found in the culture media of two GCTSC and two osteosarcoma-derived cells. M-CSF was detected in all culture media. GCTSC express CaSR, and stimulation of GCTSC with either extracellular Ca2+ or neomycin, agonist of CaSR, augumented the expression of RANKL. Some lines of GCTSC expressed alkaline phosphatase, osteocalcin and Cbfa1, suggesting that GCTSC are intimately related to osteoblastic lineage. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Moderate Alcohol Intake in Humans Attenuates Monocyte Inflammatory Responses: Inhibition of Nuclear Regulatory Factor Kappa B and Induction of Interleukin 10ALCOHOLISM, Issue 1 2006Pranoti Mandrekar Background: In contrast to the deleterious effects of chronic excessive alcohol consumption on the liver and cardiovascular system, modest alcohol intake, such as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is known about the length of time or the amounts of alcohol consumed that may cause alterations in inflammatory cells such as monocytes that are crucial to atherosclerotic vascular disease. Here, we determine in vivo effects of acute alcohol consumption on inflammatory cytokine production and nuclear regulatory factor ,B (NF- ,B) binding in human monocytes. Methods: Human blood monocytes were isolated by plastic adherence before and after acute alcohol consumption (2 ml vodka/kg body weight). Lipopolysaccharide (LPS)- and superantigen-induced tumor necrosis factor , (TNF ,), interleukin (IL)-1,, and IL-10 production were then determined in monocytes by ELISA. Nuclear regulatory factor- ,B activity of monocytes before and after alcohol consumption was estimated by electromobility shift assay and promoter-driven reporter activity. I,B, was determined by Western blotting in the cytoplasmic extracts. Results: Eighteen hours after moderate alcohol consumption, we found a significant reduction in monocyte production of inflammatory mediators, TNF- , and IL-1,, in response to LPS or staphylococcal enterotoxin B stimulation. Acute alcohol consumption inhibited LPS-induced DNA binding of the p65/p50 NF- ,B in monocytes that regulates the expression of both the TNF- , and the IL-1, genes. Consistent with this, acute alcohol treatment (25 mM) significantly reduced LPS-induced activation of an NF- ,B-driven reporter gene suggesting inhibition of this proinflammatory signaling pathway. Further, LPS-induced I,B, degradation was not affected by acute alcohol consumption indicating an I,B, -independent mechanism, as observed earlier in the in vitro acute alcohol studies. In contrast, monocyte production of the anti-inflammatory cytokine, IL-10, was augmented by acute alcohol intake. Conclusions: Our findings suggest that acute alcohol consumption has dual anti-inflammatory effects that involve augmentation of IL-10 and attenuation of monocyte inflammatory responses involving inhibition of NF- ,B. These mechanisms may contribute to the beneficial effects of moderate alcohol use on atherosclerosis. [source] Acute Alcohol Inhibits the Induction of Nuclear Regulatory Factor ,B Activation Through CD14/Toll-Like Receptor 4, Interleukin-1, and Tumor Necrosis Factor Receptors: A Common Mechanism Independent of Inhibitory ,B, Degradation?ALCOHOLISM, Issue 11 2002Pranoti Mandrekar Background Nuclear translocation and DNA binding of the nuclear factor ,B (NF-,B) is an early event in inflammatory cell activation in response to stimulation with bacterial components or cytokines. Cell activation via different receptors culminates in a common pathway leading to NF-,B activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-,B activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-,B when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors. Methods Human peripheral blood monocytes were treated with LPS, TNF,, and IL-1, in the presence or absence of 25mM alcohol for 1 hr. NF-,B activation was determined by electrophoretic mobility shift assays using nuclear extracts. Inhibitory ,B, (I,B,) was estimated by Western blotting in cytoplasmic extracts. Chinese hamster ovary cells expressing human CD14 were treated with LPS in the presence or absence of alcohol to study NF-,B and I,B, regulation. Results Our results indicate that acute alcohol inhibits IL-1,- and TNF,-induced NF-,B activation. We further show in CD14/toll-like receptor 4,expressing Chinese hamster ovary cells the specificity of alcohol-mediated inhibition of NF-,B via the toll-like receptor 4/CD14 receptors. Inhibition of NF-,B by acute alcohol was concomitant with decreased levels of the I,B, molecule in the cytoplasm of LPS, IL-1, and TNF,-activated monocytes. Conclusions These data suggest a unique, I,B,-independent pathway for the inhibition of NF-,B activation by acute alcohol in monocytes. Universal inhibition of NF-,B by acute alcohol via these various receptor systems suggests a target for the effects of alcohol in the NF-,B activation cascade that is downstream from I,B, degradation. Further, these results demonstrate that acute alcohol is a potent inhibitor of NF-,B activation by mediators of early (LPS) or late (IL-1, TNF,) stages of inflammation in monocytes. [source] Alcohol-Induced Up-Regulation of Fibrinolytic Activity and Plasminogen Activators in Human MonocytesALCOHOLISM, Issue 8 2002Edlue M. Tabengwa Background Moderate alcohol consumption is associated with reduced risk for coronary heart disease. This may due, in part to increased fibrinolysis. Monocytes synthesize fibrinolytic proteins, tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and their receptors. These studies were carried out to determine the effect of low alcohol on monocyte fibrinolytic activity and PA messenger RNA (mRNA) synthesis. Methods Peripheral blood monocytes and U937 cells were incubated in absence/presence of low alcohol (0.1%, v/v) for various times (0,1 hr), followed by incubations in the absence of alcohol (0,24 hr) before measurement of fibrinolytic activity and PA mRNA levels (reverse transcriptase polymerase chain reaction). Results Brief exposure (15 min, 4°C) of U937 cells to low alcohol resulted in an approximately 2- to 3-fold increase (269.0 ± 5.6 fmol/1 × 106 cells versus 656.0 ± 94.0 fmol/1 × 106 cells) in fibrinolytic activity. Preincubation of U937 cells and peripheral blood monocytes in low alcohol (1 hr, 37°C) followed by incubation in the absence of alcohol (24 hr) resulted in a sustained approximately 4- to 5-fold increase (414.0 ± 174.7 vs. 965.33.0 ± 104.8 fmol/1 × 106 cells) and an approximately 3- to 4-fold (20.5 ± 2.14 vs. 74 ± 2.28 fmol/2 × 106 cells, respectively) increase in fibrinolytic activity. Preincubation of monocytes with low alcohol (1 hr, 37°C) followed by incubation in the absence of alcohol (6 hr) resulted in an approximately 5- to 6-fold (0.06 ± 0.02 vs. 0.42 ± 0.02) and an approximately 2- to 3-fold (0.89 ± 0.04 vs. 2.07 ± 0.29) increase in t-PA and u-PA mRNA (reverse transcriptase polymerase chain reaction; PA/glyceraldehyde-3-phosphate dehydrogenase ratio), respectively. Conclusions These data suggest that low alcohol exerts a rapid, direct, and sustained effect on monocyte fibrinolytic activity, which may be, due in part, to increased monocyte t-PA/u-PA expression. These data provide a feasible molecular mechanism by which alcohol effects on monocyte fibrinolysis may contribute to the cardioprotective benefit associated with moderate alcohol consumption. [source] Plasminogen on the surfaces of fibrin clots prevents adhesion of leukocytes and plateletsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2010V. K. LISHKO Summary.,Background and Objectives: Although leukocytes and platelets adhere to fibrin with alacrity in vitro, these cells do not readily accumulate on the surfaces of fibrin clots in vivo. The difference in the capacity of blood cell integrins to adhere to fibrin in vivo and in vitro is striking and implies the existence of a physiologic antiadhesive mechanism. The surfaces of fibrin clots in the circulation are continually exposed to plasma proteins, several of which can bind fibrin and influence cell adhesion. Recently, we have demonstrated that adsorption of soluble fibrinogen on the surface of a fibrin clot results in its deposition as a soft multilayer matrix, which prevents attachment of blood cells. In the present study, we demonstrate that another plasma protein, plasminogen, which is known to accumulate in the superficial layer of fibrin, exerts an antiadhesive effect. Results: After being coated with plasminogen, the surfaces of fibrin clots became essentially non-adhesive for U937 monocytic cells, blood monocytes, and platelets. The data revealed that activation of fibrin-bound plasminogen by the plasminogen-activating system assembled on adherent cells resulted in the generation of plasmin, which decomposed the superficial fibrin layer, resulting in cell detachment under flow. The surfaces generated after the initial cell adhesion remained non-adhesive for subsequent attachment of leukocytes and platelets. Conclusion: We propose that the limited degradation of fibrin by plasmin generated by adherent cells loosens the fibers on the clot surface, producing a mechanically unstable substrate that is unable to support firm integrin-mediated cell adhesion. [source] Chemotherapeutic agents doxorubicin and epirubicin induce a procoagulant phenotype on endothelial cells and blood monocytesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2009L. L. SWYSTUN Summary.,Background: Although chemotherapy is associated with an increased risk of thrombosis, the pathogenic mechanisms by which chemotherapeutic agents exert prothrombotic effects are unclear. Objectives: In this study we explored the possibility that chemotherapeutic agents doxorubicin, epirubicin, 5-fluorouracil and methotrexate induce a procoagulant phenotype on vascular endothelial cells and/or on blood monocytes. Methods: Thrombin generation was measured in defibrinated plasma exposed to chemotherapy-treated human umbilical vein endothelial cells (HUVECs). Tissue factor activity assays were performed on chemotherapy-treated HUVECs and blood monocytes. The effects of chemotherapy drugs on phosphatidylserine exposure and the protein C pathway were also measured. Results: Exposure of defibrinated plasma to either doxorubicin- or epirubicin-treated HUVECs resulted in an increase in plasma thrombin generation. The procoagulant activity of doxorubicin- and epirubicin-treated HUVECs reflects an increase in tissue factor activity and phosphatidylserine exposure. Doxorubicin-mediated increase in tissue factor activity is related to increased levels of phosphatidylserine rather than to protein disulfide isomerase activity, and is likely to involve reactive oxygen species generation. Unlike doxorubicin, epirubicin does not have an impact on the protein C anticoagulant pathway. Interestingly, neither methotrextate nor 5-fluorouracil altered endothelial or monocyte hemostatic properties. Conclusions: These studies suggest that doxorubicin and epirubicin have the greatest ,prothrombotic potential' by virtue of their ability to alter endothelial and monocyte hemostatic properties. [source] Functional immaturity of cord blood monocytes as detected by impaired response to hepatocyte growth factorPEDIATRICS INTERNATIONAL, Issue 4 2001Qi Jiang AbstractBackground: Monocytes as antigen-presenting cells play an important role in host defense and transplantation. However, there are little reports on cord blood monocytes, and the role of monocytes in cord blood transplantation is largely unknown. Methods and Results: There are several cytokines affecting monocyte function. These include interferon-,, interleukin-4, interleukin-10, granulocyte macrophage-colony stimulating factor and hepatocyte growth factor (HGF). We investigated the effect of these cytokines on antigen-presenting capacity (APC) of cord and adult blood monocytes. Using either mononuclear cells or purified CD4+ T cells as responder cells, HGF enhanced APC of adult monocytes most effectively among these cytokines. In contrast, cord blood monocytes failed to respond to HGF. As HLA, costimulatory and adhesion molecules may affect APC function, we examined these antigens of monocytes following HGF stimulation. The HGF upregulated integrin ,5 subunit (CD49e) and intercellular adhesion molecule-1 (CD54) was expressed in adult blood monocytes, but not in cord blood. In kinetic studies, HGF downregulated c-met protein/HGF receptor expression of adult monocytes in lower concentrations and at shorter incubation time as compared with that of cord blood. Conclusions: The results suggest that impaired response of cord blood monocytes to HGF may be responsible, in large part, for their functional immaturity. [source] Hericium erinaceum induces maturation of dendritic cells derived from human peripheral blood monocytesPHYTOTHERAPY RESEARCH, Issue 1 2010Sun Kyung Kim Abstract Hericium erinaceum, a medicinal mushroom, has long been used as a therapeutic due to its immuno-regulating potentials eliciting anticarcinogenic and antimicrobial efficacies. Since maturation of dendritic cells (DC) is an important process in the initiation and regulation of immune responses, the ability of water-soluble components from H. erinaceum (WEHE) to regulate DC maturation was investigated. Immature DC were prepared by differentiating human peripheral blood CD14-positive cells with GM-CSF and IL-4. DC were stimulated with WEHE at 2,20 µg/mL for 48 h and subjected to flow cytometric analysis to determine the expression of indicative maturation markers. The endocytic capacity of WEHE-stimulated DC was examined by a Dextran-FITC uptake assay. An enzyme-linked immunosorbent assay was performed to examine the secretion of TNF- , and IL-12p40. DC stimulated with WEHE showed representative features upon DC maturation: enhanced expression of CD80, CD83 and CD86, and both MHC class I and II molecules, decreased endocytic capacity of DC, increased expression of CD205, and decreased expression of CD206. However, interestingly, WEHE could not induce the production of TNF- , and IL-12p40, whereas lipopolysaccharide substantially increased the production of both cytokines. Collectively, these results suggest that H. erinaceum induces the maturation of human DC, which might reinforce the host innate immune system. Copyright © 2009 John Wiley & Sons, Ltd. [source] Protein-induced changes during the maturation process of human dendritic cells: A 2-D DIGE approachPROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2008Gabriela Bomfim Ferreira Abstract Dendritic cells (DCs) are unique antigen presenting cells, which upon maturation change from a specialized antigen-capturing cell towards a professional antigen presenting cells. In this study, a 2-D DIGE analysis of immature and mature DCs was performed, to identify proteins changing in expression upon maturation. The protein expression profile of immature and mature DCs, derived from CD14+ peripheral blood monocytes was investigated using two pH ranges (pH,4,7 and 6,9) (n,=,4). Ninety one differentially expressed spots (p<0.01) were detected, from which we identified 74 spots (81.32%) corresponding to 41 different proteins. The proteins identified play a role in diverse processes, such as antigen processing/presentation, vesicle transport and cytoskeleton remodeling. In addition, a protein interaction network contained 29 (out of 41) proteins, suggesting that, although they functionally originate from distinct classes, these proteins are acting as a protein-interactome. In conclusion, the proteins shown here to be altered in expression upon maturation are in line with the morphological and functional changes observed during the maturation process, providing a better understanding of the processes involved. This will open new avenues for investigating treatment regimens for immune-associated disorders. [source] ORIGINAL ARTICLE: Enhanced Maternal Anti-Fetal Immunity Contributes to the Severity of Hypertensive Disorder Complicating PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010Li-Ping Liu Citation Liu L-P, Huang W, Lu Y-C, Liao A-H. Enhanced maternal anti-fetal immunity contributes to the severity of hypertensive disorder complicating pregnancy. Am J Reprod Immunol 2010 Problem, The aim of this study was to evaluate how fetal monocyte activation and maternal anti-fetal antigen-specific antibody-secreting cells (ASC) affect the severity of hypertensive disorder complicating pregnancy (HDCP). Method of study, Forty-six healthy third-trimester pregnant women and 20 patients with gestational hypertension, 20 with mild pre-ecalmpsia and another 20 with severe pre-eclampsia were included in the study. Interleukin-6 (IL-6) release from cord blood monocytes was examined by intracellular cytokine staining and flow cytometric analysis. Moreover, the maternal anti-fetal antigen-specific ASC were detected by enzyme-linked immunospot assay. Results, A significantly increased percentage of IL-6-positive monocytes were detected in the cord blood of study groups compared with the controls (P < 0.01). The percentage of IL-6-positive monocytes was increased as the disease progressed (P < 0.05). There were more anti-fetal antigen-specific ASC in the study groups than those in the controls (P < 0.001). Furthermore, the anti-fetal antigen-specific ASC showed difference in gestational hypertensive and severe pre-eclamptic groups (P < 0.05). Conclusion, We conclude that the fetal monocyte activation and the increase in maternal anti-fetal antigen-specific ASC were related to the incidence and severity of HDCP. These results provide both indirect and direct evidence for the occurrence of exaggerated maternal humoral immunity against the fetal antigens in HDCP. [source] Circulating Toll-like receptor (TLR) 2, TLR4, and regulatory T cells in patients with chronic hepatitis CAPMIS, Issue 4 2010JIU-PING WANG Wang J-P, Zhang Y, Wei X, Li J, Nan X-P, Yu H-T, Li Y, Wang P-Z, Bai X-F. Circulating Toll-like receptor (TLR) 2, TLR4, and regulatory T cells in patients with chronic hepatitis C. APMIS 2010; 118: 261,70. The mechanism of hepatitis C virus (HCV) involvement in innate immune responses and immune modulation has not been well characterized. In the present work, we studied Toll-like receptor (TLR) 2 and TLR4, which were recently recognized as the important components of innate immunity, as well as CD4+ CD25+ CD127low/, regulatory T cells (Tregs), which actively suppress pathological and physiological immune response during HCV infection. The study involved 31 chronic hepatitis C patients and 20 healthy controls. TLR2 and TLR4 expression in peripheral blood monocytes and the number of Tregs were examined by flow cytometric analysis. Overexpression of TLR2 and TLR4 was found in chronic hepatitis C patients as compared with controls. Furthermore, increased cytokine production, including that of ,-interferon, tumor necrosis factor-,, interleukin (IL)-6, and IL-8, was observed in peripheral blood mononuclear cells from chronic hepatitis C patients after challenge with TLR2 and TLR4 agonists. The number of Tregs was significantly higher in chronic hepatitis C patients and the increased Tregs were associated with HCV genotype 1b. In vitro studies demonstrated that circulating Tregs suppress T-cell responses in chronic hepatitis C patients. Significant correlations were found between the viral load and Treg number and between TLR2 and TLR4 level in chronic hepatitis C patients. Taken together with other published data, these results suggest that TLR2, TLR4, and Tregs correlate closely with chronic HCV infection. [source] Effects of arsenobetaine, a major organic arsenic compound in seafood, on the maturation and functions of human peripheral blood monocytes, macrophages and dendritic cellsAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 9 2004Takami Ohta Abstract We examine the in vitro immunotoxicity of synthetically pure arsenobetaine [AsBe; trimethyl (carboxymethyl) arsonium zwitterion], which is a major organic arsenic compound in seafood, on various human immune cells, such as peripheral blood monocytes, monocyte-derived macrophages and monocyte-derived dendritic cells (DCs). In particular, we examine the differentiation of monocytes into macrophages or DCs by comparing the effects of AsBe with those pentavalent inorganic arsenate. AsBe neither enhanced nor inhibited the differentiation of human monocytes into macrophages or DCs, and also did not affect their various immune functions. Furthermore, AsBe had no cytolethality in monocyte-derived macrophages or DCs even at a concentration of 5 mmol l,1. In contrast, inorganic arsenate showed strong cytolethality in these human immune cells in vitro at micromolar concentrations. These data indicate that the organic arsenic compound AsBe in seafood has no in vitro immunotoxicity in human immune cells. Copyright © 2004 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||