Home About us Contact
|
Home About us Contact | ||
|
|
||
Neutrophil Chemotaxis (neutrophil + chemotaxis)
Selected Abstracts2-Phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole Derivatives: New Potent Inhibitors of fMLP-Induced Neutrophil Chemotaxis.CHEMINFORM, Issue 43 2007Olga Bruno Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Airway inflammation: chemokine-induced neutrophilia and the class,I phosphoinositide 3-kinasesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2005Matthew Abstract Class,I phosphoinositide 3-kinases (PI3K) are known to play a significant role in neutrophil chemotaxis. However, the relative contributions of different PI3K isoforms, and how these impact on lung inflammation, have not been addressed. In vitro studies using wild-type and PI3K, knockout neutrophils demonstrated the major role of the ,,isoform in chemotactic but not chemokinetic events. This was confirmed by a model of direct chemokine instillation into the airways in vivo. Within all studies, a low yet significant degree of neutrophil movement in the absence of PI3K, could be observed. No role for the ,,isoform was demonstrated both in vitro and in vivo using PI3K, kinase-dead knock-in mice. Moreover, further studies using the broad-spectrum PI3K inhibitors wortmannin or LY294002 showed no other class,I PI3K isoforms to be involved in these chemotactic processes. Here, we identify a contributory PI3K-independent mechanism of neutrophil movement, yet demonstrate PI3K, as the pivotal mediator through which the majority of neutrophils migrate into the lung in response to chemokines. These data resolve the complexities of chemokine-induced neutrophilia and PI3K signaling and define the ,,isoform as a promising target for new therapeutics to treat airway inflammatory diseases. [source] Key role of proline-rich tyrosine kinase 2 in interleukin-8 (CXCL8/IL-8)-mediated human neutrophil chemotaxisIMMUNOLOGY, Issue 4 2004Vito Di Cioccio Summary The signalling pathways leading to CXCL8/IL-8-induced human neutrophil migration have not been fully characterized. The present study demonstrates that CXCL8 induces tyrosine phosphorylation as well as enzymatic activity of proline-rich tyrosine kinase 2 (Pyk2), a non-receptor protein tyrosine kinase (PTK), in human neutrophils. Induction of Pyk2 tyrosine phosphorylation by CXCL8 is regulated by Src PTK activation, whereas it is unaffected by phosphatidylinositol 3-kinase activation. Inhibition of Pyk2 activation by PP1, a Src PTK inhibitor, is paralleled by the inhibition of CXCL8-mediated neutrophil chemotaxis. Among CXCL8 receptors, Src protein tyrosine kinase activation selectively regulates CXCR1-mediated polymorphonuclear neutrophil (PMN) chemotaxis. Overexpression of PykM, the kinase-dead mutant of Pyk2, blocks CXCL8-induced chemotaxis of HL-60-derived PMN-like cells, thus pinpointing the key role of Pyk2 in CXCL8-induced chemotaxis. [source] Extensive xanthelasma associated with anaplastic large cell lymphoma and hyperimmunoglobulin E syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2003Mi-Woo Lee MD A 57-year-old woman presented with a 6-month history of an extensively spreading, yellowish patch on the periorbital areas and cheeks. A diagnosis of hyperimmunoglobulin E syndrome had been made at the age of 22 years on the basis of an eczematous eruption, recurrent furunculosis, and a persistently elevated immunoglobulin E (IgE) level. Her past medical history revealed that she had suffered from numerous recurrent bouts of chronic sinusitis, otitis media, oral candidiasis, orbital cellulitis, acne rosacea, and pneumonia caused by cytomegalovirus since her twenties. In addition, 1 year ago, anaplastic large cell lymphoma of the cervical lymph node (stage IIIb) developed, and she received six cycles of cyclophosphamide,doxorubicin,vincristine,prednisolone (CHOP) chemotherapy with partial remission. None of her family had any of these problems. Cutaneous examination showed extensive, symmetric, noninfiltrated macular areas of distinct yellow discoloration around the eyes and on both cheeks (Fig. 1). There were also erythematous papulonodular eruptions on the nose and both cheeks, which were thought to be acne rosacea. Laboratory findings were normal, except for an elevated IgE level (8157 IU/mL). Serum concentrations of IgG, IgA, and IgM were normal. Serum complement levels were normal, as evidenced by normal C3, C4, and CH50. Although she had a previous history of a decreased level (12%) of nitroblue tetrazolium (NBT) test (control, 53%), NBT test at our institute was normal. Neutrophil function tests, including neutrophil chemotaxis, neutrophil phagocytosis, neutrophil respiratory burst, and neutrophil microbial killing test, by flow cytometry, showed normal results. The serum lipid levels, including total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were normal. Serum lipoprotein electrophoresis was normal. A biopsy specimen revealed scattered foamy cells throughout the dermis. The larger clusters of foamy cells tended to group around the blood vessels of the dermis (Fig. 2). Figure 1. Extensively distributed, yellowish, flat xanthelasma on the face Figure 2. Clusters of foamy cells around the blood vessels of the dermis (hematoxylin and eosin, ×400) [source] Microbiological, immunological and genetic factors in family members with periodontitis as a manifestation of systemic disease, associated with hematological disordersJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2002Mitsugi Okada The microflora, immunological profiles of host defence functions, and human leukocyte antigen (HLA) findings are reported for a mother, son and daughter who were diagnosed as having ,periodontitis as a manifestation of systemic diseases, associated with hematological disorders'. Examinations were made of the bacterial flora from the periodontal pocket, neutrophil chemotaxis, neutrophil phagocytosis, and the genotypes (DQB1) and serotypes (DR locus) of HLA class II antigens. Phenotypic analyses of the peripheral lymphocytes were also conducted. The subgingival microflora from the mother was dominated by Gram-negative rods, especially Porphyromonas endodontalis, Prevotella intermedia/Prevotella nigrescens and Fusobacterium nucleatum. Subgingival microflora samples from the son and daughter were dominated by Gram-positive cocci and Gram-positive rods. Through the use of polymerase chain reaction, Campylobacter rectus and Capnocytophaga gingivalis were detected in all subjects, whereas Porphyromonas gingivalis, P. intermedia, and Treponema denticola were not detected in any subjects. All three subjects showed a remarkable level of depressed neutrophil chemotaxis to N-formyl-methionyl-leucyl-phenylalanine, although their phagocyte function levels were normal, in comparison to healthy control subjects. Each subject had the same genotype, HLA-DQB1*0601, while the mother had HLA-DR2 and HLA-DR8, and the son and daughter had HLA-DR2 only. In summary, the members of this family showed a similar predisposition to periodontitis with regard to certain host defence functions. It is suggested that the depressed neutrophil chemotaxis that was identified here could be a significant risk factor for periodontitis in this family. [source] Role of Complement Anaphylatoxin C3a in Photodynamic Therapy-elicited Engagement of Host Neutrophils and Other Immune CellsPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2006Ivana Cecic ABSTRACT Tumor treatment by photodynamic therapy (PDT) provokes a host-protective inflammatory and acute-phase response and an immune reaction. Neutrophilia manifested in this context is driven by multiple mediators of neutrophil chemotaxis orchestrated by an activated complement system. Mouse FsaR fibrosarcoma was used in this study to further investigate neutrophilia induced by Photofrin-based PDT. The complement anaphylatoxin C3a was identified as a major chemo-attractant in the advanced phase of PDT-induced neutrophilia, because injecting mice with antibodies blocking its receptor C3aR significantly inhibited the increase in neutrophil levels 8 h after PDT. At the same time point, an increased C3aR expression was detected in neutrophils, monocytes and B lymphocytes in the blood of host mice. Peritoneal macro-phages and mast cells harvested from treatment-naive mice exhibited elevated C3aR expression after coincubation in vitro for 8 h with PDT-treated FsaR cells. Thus, C3a emerges as one of the key effector molecules engaged in PDT-induced host response. [source] Neutrophil dysfunction in a family with a SAPHO syndrome,like phenotypeARTHRITIS & RHEUMATISM, Issue 10 2008Polly J. Ferguson SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is an inflammatory disorder of the bone, skin, and joints. We describe a family with multiple affected members who segregate a SAPHO syndrome,like phenotype, and we report the results of neutrophil studies and candidate gene analysis. We obtained written informed consent and a family history and reviewed medical records. We collected DNA and sequenced candidate genes, and we performed functional studies on neutrophils isolated from the proband and her mother. The pedigree segregated chronic osteomyelitis and cutaneous inflammation in a pattern that suggested an autosomal-dominant disorder. No coding sequence mutations were detected in PSTPIP1,PSTPIP2, LPIN2, SH3BP2, or NCF4. Analysis of neutrophil function in the proband, including nitroblue tetrazolium tests, myeloperoxidase assays, neutrophil chemotaxis, and neutrophil chemotaxis assays, revealed no identifiable abnormalities. However, an abnormality in the luminol, but not the isoluminol, respiratory burst assays following stimulation with phorbol myristate acetate (PMA) was detected in neutrophils isolated from the affected proband. Internal oxidant production was also reduced in the proband and her mother when neutrophils were treated with fMLP with or without platelet-activating factor, PMA alone, or tumor necrosis factor , alone. This family segregates a disorder characterized by chronic inflammation of the skin and bone. Functional differences in neutrophils exist between affected individuals and controls. The biologic significance of this defect remains unknown. Identification of the gene defect will help identify an immunologic pathway that, when dysregulated, causes inflammation of the skin and bone. [source] Blockade of parathyroid hormone,related protein prevents joint destruction and granuloma formation in streptococcal cell wall,induced arthritisARTHRITIS & RHEUMATISM, Issue 6 2003J. L. Funk Objective To determine whether parathyroid hormone,related protein (PTHrP), an interleukin-1,,inducible, bone-resorbing peptide that is produced in increasing amounts by the synovium in rheumatoid arthritis (RA), may play a role in the pathophysiology of joint destruction in RA. Methods PTHrP expression and the effect of PTHrP 1,34 neutralizing antibody on disease progression were tested in streptococcal cell wall (SCW),induced arthritis, an animal model of RA. Results As has been reported in RA, while serum levels of PTHrP did not change during SCW-induced arthritis, PTHrP expression dramatically increased in the arthritic synovium. Treatment with PTHrP neutralizing antibody (versus control antibody) did not affect joint swelling in SCW-treated animals. However, PTHrP antibody significantly inhibited SCW-induced joint destruction, as measured by its ability to block increases in serum pyridinoline (a marker of cartilage and bone destruction), erosion of articular cartilage, decreases in femoral bone mineral density, and increases in the numbers of osteoclasts in eroded bone. Unexpectedly, granuloma formation at sites of SCW deposition in the liver and spleen was also inhibited by PTHrP antibody, an effect associated with significant decreases in the tissue influx of PTH/PTHrP receptor,positive neutrophils and in SCW-induced neutrophilia. In vitro, neutrophil chemotaxis was stimulated by PTHrP 1,34. Conclusion These findings suggest that PTHrP, consistent with its previously described osteolytic effects in metastatic bone disease, can also be an important mediator of joint destruction in inflammatory bone disorders, such as RA. Moreover, this study reveals heretofore unknown effects of PTHrP peptides on neutrophil function that could have important implications in the pathogenesis of inflammatory granulomatous disorders. [source] Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human ,-defensins from neutrophilsBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2007Y. Zheng Summary Background, Psoriasis is characterized by epidermal infiltration of neutrophils that destroy invading microorganisms via a potent antimicrobial arsenal of oxidants and antimicrobial agents. In contrast to atopic dermatitis, psoriasis exhibits low levels of skin infections due to the presence of antimicrobial agents, including cathelicidin LL-37. LL-37 kills a broad spectrum of microbes, and activates neutrophil chemotaxis. Objective, To determine whether or not LL-37 could regulate additional neutrophil functions such as production of cytokines/chemokines, reactive oxygen species and release of neutrophil antimicrobial peptides. Methods, Human peripheral blood neutrophils were used in this study. The production of interleukin (IL)-8 and release of ,-defensins were analysed by enzyme-linked immunosorbent assay, and real-time polymerase chain reaction (PCR) was used to quantify ,-defensin gene expression. Phosphorylation of mitogen-activated protein kinase (MAPK) was determined by Western blotting. The generation of reactive oxygen species was examined using flow cytometry, and intracellular Ca2+ mobilization was measured using a calcium assay kit. Results, LL-37 enhanced the production of IL-8 under the control of MAPK p38 and extracellular signal regulated kinase (ERK), as evidenced by the inhibitory effects of p38 and ERK1/2 inhibitors on LL-37-mediated IL-8 production. Furthermore, LL-37 induced phosphorylation of p38 and ERK. We also revealed that LL-37 stimulated the generation of reactive oxygen species dose- and time-dependently, most probably via NADPH oxidase activation and intracellular Ca2+ mobilization. Finally, LL-37 induced both mRNA expression and protein release of ,-defensins, known as human neutrophil peptide 1,3. Conclusion, Taken together, we suggest that in addition to its microbicidal properties, LL-37 may contribute to innate immunity by enhancing neutrophil host defence functions at inflammation and/or infection sites. [source] | ||||||||||||||||||||||