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Monocyte Adhesion (monocyte + adhesion)
Terms modified by Monocyte Adhesion Selected AbstractsThe p110, Isoform of PI3K Differentially Regulates ,1 and ,2 Integrin-Mediated Monocyte Adhesion and Spreading and Modulates DiapedesisMICROCIRCULATION, Issue 6 2006ALEXANDER M. FERREIRA ABSTRACT Objective: Leukocyte diapedesis is misregulated in inflammatory disease and depends on the binding of monocytic LFA-1 and VLA-4 to endothelial ICAM-1 and VCAM-1, respectively. The authors hypothesized that these different molecular interactions elicit specific signaling cascades within monocytes regulating specific steps in adhesion, motility, and diapedesis. Methods: The authors employed the PI3K p110, catalytic subunit specific inhibitor IC87114 (2 , M) and the broad-spectrum PI3K inhibitory agents LY294002 (50 , M) and wortmannin (100 nM), to examine the role of PI3K, in monocyte diapedesis through endothelial monolayers and its role in monocyte adhesion and spreading upon carpets of ICAM-1 or VCAM-1. They further explored the effects of PI3K, inhibition on the activation state of , 1 and , 2 integrins with immunocytochemistry and flow cytometry. Results: In human peripheral blood monocytes IC87114 was as effective as wortmannin and LY294002 at inhibiting diapedesis, however, in THP-1 cells LY294002 and wortmannin caused a 5-fold reduction in diapedesis, while IC87114 only decreased diapedesis 2-fold. PI3K, activity was specifically required for THP-1 cell adhesion and spreading on VCAM-1, but not on ICAM-1 protein substrates. Flow cytometric analysis demonstrated that PI3K, inhibition decreased the amount of conformationally active , 1-integrins, while having no effect on the prevalence of conformationally active , 2-integrins expressed on the cell surface. In addition, PI3K, inhibition resulted in a 4-fold decrease in the activation state of Rac-1 and Cdc42. Conclusions: These results demonstrate the specific necessity of PI3K, in regulating monocytic integrin activation and the general role of PI3K signaling during diapedesis, implicating PI3K as a target for therapeutic intervention. [source] S -Allyl- L -Cysteine Sulfoxide Inhibits Tumor Necrosis Factor-Alpha Induced Monocyte Adhesion and Intercellular Cell Adhesion Molecule-1 Expression in Human Umbilical Vein Endothelial CellsTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2010Chai Hui Abstract Garlic and its water-soluble allyl sulfur-containing compound, S -Allyl- L -cysteine Sulfoxide (ACSO), have shown antioxidant and anti-inflammatory activities, inhibiting the development of atherosclerosis. However, little is known about the mechanism(s) underlying the therapeutic effect of ACSO in inhibiting the formation of atherosclerostic lesion. This study aimed to investigate whether ACSO could modulate tumor necrosis factor-alpha (TNF-,)-induced expression of intercellular cell adhesion molecule-1, monocyte adhesion and TNF-,-mediated signaling in human umbilical vein endothelial cells. While TNF-, promoted the intercellular cell adhesion molecule-1 mRNA transcription in a dose- and time-dependent manner, ACSO treatment significantly reduced the levels of TNF-,-induced intercellular cell adhesion molecule-1 mRNA transcripts (P < 0.01). Furthermore, ACSO dramatically inhibited TNF-, triggered adhesion of THP-1 monocytes to endothelial cells and porcine coronary artery rings. Moreover, ACSO mitigated TNF-, induced depolarization of mitochondrial membrane potential and overproduction of superoxide anion, associated with the inhibition of NOX4, a subunit of nicotinamide adenine dinucleotide phosphate-oxidase, mRNA transcription. In addition, ACSO also inhibited TNF-,-induced phosphorylation of JNK, ERK1/2 and I,B, but not p38. Apparently, ACSO inhibited proinflammatory cytokine-induced adhesion of monocytes to endothelial cells by inhibiting the mitogen-activated protein kinase signaling and related intercellular cell adhesion molecule-1 expression, maintaining mitochondrial membrane potential, and suppressing the overproduction of superoxide anion in endothelial cells. Therefore, our findings may provide new insights into ACSO on controlling TNF-,-mediated inflammation and vascular disease. Anat Rec, 2010. © 2010 Wiley-Liss, Inc. [source] Enhanced monocyte binding to human cytomegalovirus-infected syncytiotrophoblast results in increased apoptosis via the release of tumour necrosis factor alphaTHE JOURNAL OF PATHOLOGY, Issue 4 2005Gary Chan Abstract We have shown that monocytes bound to intercellular adhesion molecules (ICAM-1) on syncytialized placental trophoblasts (ST) induce trophoblast apoptosis, and that ST infection by human cytomegalovirus (HCMV) up-regulates ICAM-1. We hypothesize that the focal loss of trophoblast seen in HCMV-infected placenta is mediated by increased adherence of monocytes at sites of infection. We find that ST cultures (differentiated from primary cytotrophoblasts) increase monocyte binding when infected with HCMV. Monocyte adhesion was inhibited by antibodies to ICAM-1 and its ligand leukocyte function-associated molecule (LFA-1) on monocytes. When co-cultured with adhering monocytes, infected ST cultures had higher levels of apoptosis than infected cultures alone. Although trophoblast apoptosis clustered around adhering monocytes, it occurred only in non-infected cells. Blocking monocyte binding with ICAM-1 and LFA-1 antibodies reduced the rate of apoptosis to that of the infected culture. Co-cultures incubated with TNF, antibody and EGF inhibited both monocyte- and HCMV-induced apoptosis but did not block binding. We conclude that HCMV stimulates ST culture expression of ICAM-1, which binds to LFA-1 on monocytes that release TNF,, thereby inducing apoptosis of neighbouring uninfected trophoblasts. The above data indicates that trophoblast loss associated with HCMV infection can be caused by increased monocyte adhesion to ST. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Cardiovascular pharmacology and physiology of the isoprostanesFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2006Jean-Luc Cracowski Abstract F2 -isoprostanes are a complex family of compounds produced from arachidonic acid via a free radical-catalyzed mechanism. Their quantification as a pathophysiological biomarker provides a unique opportunity to investigate lipid peroxidation in vascular diseases. Their measurement also provides an interesting biomarker for the rational dose selection of antioxidants in vascular diseases where oxidative stress might be involved. In addition to their use as biomarkers, some isoprostanes possess a biological activity. The 15-series F2 - and E2 -isoprostanes mediate vasoconstriction in different vascular beds and species. In addition, 15-F2t -IsoP induces smooth muscle cells mitogenesis and monocyte adhesion to endothelial cells. The data available supports but does not prove the hypothesis that isoprostanes are involved in vascular physiology and pathogenesis. [source] Butyrate inhibits leukocyte adhesion to endothelial cells via modulation of VCAM-1INFLAMMATORY BOWEL DISEASES, Issue 2 2004Thomas Menzel MD Abstract Background Leukocyte recruitment to areas of inflammation depends on Integrin-VCAM/ICAM interaction. Blocking the vascular cell adhesion molecule (VCAM-1) and the intracellular adhesion molecule (ICAM-1) may have therapeutic benefit for the inflammatory component of bowel disease. Notably, the induction of ICAM and VCAM is mediated by a nuclear factor kappaB (NF-,B)-dependent mechanism. We investigated whether the anti-inflammatory properties of butyrate are mediated via the modulation of VCAM and ICAM on human endothelial cells. Methods VCAM-1 and ICAM-1 expression on human endothelial cells upon tumor necrosis factor-, (TNF-,) stimulation was assessd by FACS analysis. A monocyte adhesion assay was performed to evaluate the relevance of a modulated CAM-expression. Electrophoretic mobility shift assays were applied to investigate NF-,B activation. Results The observed butyrate-associated inhibition of monocyte adhesion to endothelial cells is associated with an inhibition of NF-,B activation in human endothelial cells. In this context, the observed suppression of the TNF-, induced VCAM-1 expression is likely to play an essential role. Conclusions Butyrate inhibits VCAM-1 mediated leukocyte adhesion to human endothelial cells. This inhibition may contribute to the anti-inflammatory effects of butyrate in patients with distal ulcerative colitis. [source] Role of LOX-1 in monocyte adhesion-triggered redox, Akt/eNOS and Ca2+ signaling pathways in endothelial cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2009Nobuo Sakamoto This study was conducted to examine the role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in monocyte adhesion-induced redox-sensitive, Akt/eNOS and Ca2+ signaling pathways in endothelial cells (ECs). LOX-1 was blocked by an antibody-neutralizing LOX-1 TS92 or small interfering RNA. In cultured human aortic ECs, monocyte adhesion activated Rac1 and p47phox, and increased NADPH oxidase activity and reactive oxygen species (ROS) generation within 30,min and NF-,B phosphorylation within 1,h, resulting in redox-sensitive gene expression. Akt and eNOS phosphorylation was induced 15,min after adding monocytes and returned to control level after 30,min, whereas NO production was not altered by monocyte adhesion. Blockade of LOX-1 blunted the monocyte adhesion-triggered redox-sensitive signaling pathway and Akt/eNOS phosphorylation in ECs. Both endothelial intracellular Ca2+ mobilization and Ca2+ influx caused by monocyte attachment were markedly attenuated by pretreatment of ECs with TS92. This suggests that LOX-1 is involved in redox-sensitive, Akt/eNOS and Ca2+ signaling pathways in monocyte adhesion to ECs independent of oxidized low-density lipoprotein (ox-LDL). Furthermore, blockade of Ca2+ inhibited monocyte adhesion-triggered Rac1 and p47phox activation and ROS generation in ECs, whereas Ca2+ signaling was suppressed by blockade of NADPH oxidase and ROS generation. Finally, TS92 blocked the monocyte adhesion to ECs stimulated with or without tumor necrosis factor-, or ox-LDL. We provide evidence that LOX-1 plays a role in redox-sensitive, Akt/eNOS and Ca2+ signaling pathways in monocyte adhesion to ECs independent of the ox-LDL,LOX-1 axis. J. Cell. Physiol. 220: 706,715, 2009. © 2009 Wiley-Liss, Inc. [source] The p110, Isoform of PI3K Differentially Regulates ,1 and ,2 Integrin-Mediated Monocyte Adhesion and Spreading and Modulates DiapedesisMICROCIRCULATION, Issue 6 2006ALEXANDER M. FERREIRA ABSTRACT Objective: Leukocyte diapedesis is misregulated in inflammatory disease and depends on the binding of monocytic LFA-1 and VLA-4 to endothelial ICAM-1 and VCAM-1, respectively. The authors hypothesized that these different molecular interactions elicit specific signaling cascades within monocytes regulating specific steps in adhesion, motility, and diapedesis. Methods: The authors employed the PI3K p110, catalytic subunit specific inhibitor IC87114 (2 , M) and the broad-spectrum PI3K inhibitory agents LY294002 (50 , M) and wortmannin (100 nM), to examine the role of PI3K, in monocyte diapedesis through endothelial monolayers and its role in monocyte adhesion and spreading upon carpets of ICAM-1 or VCAM-1. They further explored the effects of PI3K, inhibition on the activation state of , 1 and , 2 integrins with immunocytochemistry and flow cytometry. Results: In human peripheral blood monocytes IC87114 was as effective as wortmannin and LY294002 at inhibiting diapedesis, however, in THP-1 cells LY294002 and wortmannin caused a 5-fold reduction in diapedesis, while IC87114 only decreased diapedesis 2-fold. PI3K, activity was specifically required for THP-1 cell adhesion and spreading on VCAM-1, but not on ICAM-1 protein substrates. Flow cytometric analysis demonstrated that PI3K, inhibition decreased the amount of conformationally active , 1-integrins, while having no effect on the prevalence of conformationally active , 2-integrins expressed on the cell surface. In addition, PI3K, inhibition resulted in a 4-fold decrease in the activation state of Rac-1 and Cdc42. Conclusions: These results demonstrate the specific necessity of PI3K, in regulating monocytic integrin activation and the general role of PI3K signaling during diapedesis, implicating PI3K as a target for therapeutic intervention. [source] Effect of isoflurane on monocyte adhesion molecule expression in human whole blood,ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2003L. W. De Rossi Background: Recruitment of monocytes to inflamed tissue is a crucial step in the acute inflammatory reaction. Adherence of monocytes to endothelial cells followed by transmigration depends on monocyte surface adhesion molecules, inflammatory cytokines and chemoattractant chemokines. In the present study, we determined the effect of isoflurane on monocyte adhesion receptor expression in vitro. Methods: Citrated whole blood was incubated for 60 min with either 0.5 or 1 MAC isoflurane. In unstimulated blood samples and after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP) monocyte cell-surface expression of the selectins PSGL-1 and L-selectin, and the ,2 -integrins CD11a and CD11b were evaluated by flow cytometry. Results: Isoflurane reduced significantly the expression of PSGL-1 on unstimulated monocytes, whereas the remaining selectins and ,2 -integrins were not affected. At both concentrations, the FMLP-induced removal of PSGL-1 from the monocyte surface was increased. Furthermore, at 1 MAC isoflurane the FMLP-induced increase in CD11a expression was significantly inhibited. The surface expression of L-selectin and CD11b was not affected following exposure to isoflurane. Conclusion: Isoflurane increases the removal of the selectin PSGL-1 from the monocyte surface. Since PSGL-1 is important during the initial step of monocyte adhesion to endothelial P-selectin, the decrease in monocyte surface PSGL-1 may have profound effects on monocyte,endothelial interactions. Furthermore, the effects of isoflurane on monocyte adhesion molecule expression are different from those reported for neutrophils. [source] S -Allyl- L -Cysteine Sulfoxide Inhibits Tumor Necrosis Factor-Alpha Induced Monocyte Adhesion and Intercellular Cell Adhesion Molecule-1 Expression in Human Umbilical Vein Endothelial CellsTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2010Chai Hui Abstract Garlic and its water-soluble allyl sulfur-containing compound, S -Allyl- L -cysteine Sulfoxide (ACSO), have shown antioxidant and anti-inflammatory activities, inhibiting the development of atherosclerosis. However, little is known about the mechanism(s) underlying the therapeutic effect of ACSO in inhibiting the formation of atherosclerostic lesion. This study aimed to investigate whether ACSO could modulate tumor necrosis factor-alpha (TNF-,)-induced expression of intercellular cell adhesion molecule-1, monocyte adhesion and TNF-,-mediated signaling in human umbilical vein endothelial cells. While TNF-, promoted the intercellular cell adhesion molecule-1 mRNA transcription in a dose- and time-dependent manner, ACSO treatment significantly reduced the levels of TNF-,-induced intercellular cell adhesion molecule-1 mRNA transcripts (P < 0.01). Furthermore, ACSO dramatically inhibited TNF-, triggered adhesion of THP-1 monocytes to endothelial cells and porcine coronary artery rings. Moreover, ACSO mitigated TNF-, induced depolarization of mitochondrial membrane potential and overproduction of superoxide anion, associated with the inhibition of NOX4, a subunit of nicotinamide adenine dinucleotide phosphate-oxidase, mRNA transcription. In addition, ACSO also inhibited TNF-,-induced phosphorylation of JNK, ERK1/2 and I,B, but not p38. Apparently, ACSO inhibited proinflammatory cytokine-induced adhesion of monocytes to endothelial cells by inhibiting the mitogen-activated protein kinase signaling and related intercellular cell adhesion molecule-1 expression, maintaining mitochondrial membrane potential, and suppressing the overproduction of superoxide anion in endothelial cells. Therefore, our findings may provide new insights into ACSO on controlling TNF-,-mediated inflammation and vascular disease. Anat Rec, 2010. © 2010 Wiley-Liss, Inc. [source] Enhanced monocyte binding to human cytomegalovirus-infected syncytiotrophoblast results in increased apoptosis via the release of tumour necrosis factor alphaTHE JOURNAL OF PATHOLOGY, Issue 4 2005Gary Chan Abstract We have shown that monocytes bound to intercellular adhesion molecules (ICAM-1) on syncytialized placental trophoblasts (ST) induce trophoblast apoptosis, and that ST infection by human cytomegalovirus (HCMV) up-regulates ICAM-1. We hypothesize that the focal loss of trophoblast seen in HCMV-infected placenta is mediated by increased adherence of monocytes at sites of infection. We find that ST cultures (differentiated from primary cytotrophoblasts) increase monocyte binding when infected with HCMV. Monocyte adhesion was inhibited by antibodies to ICAM-1 and its ligand leukocyte function-associated molecule (LFA-1) on monocytes. When co-cultured with adhering monocytes, infected ST cultures had higher levels of apoptosis than infected cultures alone. Although trophoblast apoptosis clustered around adhering monocytes, it occurred only in non-infected cells. Blocking monocyte binding with ICAM-1 and LFA-1 antibodies reduced the rate of apoptosis to that of the infected culture. Co-cultures incubated with TNF, antibody and EGF inhibited both monocyte- and HCMV-induced apoptosis but did not block binding. We conclude that HCMV stimulates ST culture expression of ICAM-1, which binds to LFA-1 on monocytes that release TNF,, thereby inducing apoptosis of neighbouring uninfected trophoblasts. The above data indicates that trophoblast loss associated with HCMV infection can be caused by increased monocyte adhesion to ST. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Monocyte-Induced Endothelial Calcium Signaling Mediates Early Xenogeneic Endothelial ActivationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2005Mark D. Peterson Hallmarks of delayed xenograft rejection include monocyte infiltration, endothelial cell activation and disruption of the endothelial barrier. The monocyte is an important initiator of this type of rejection because monocytes accumulate within hours after xenografting and prior monocyte depletion suppresses the development of this type of rejection. However, the mechanisms that mediate monocyte-induced xenograft injury are unclear at present. Here we report that human monocytes activate xenogeneic endothelial cells through calcium signals. Monocyte contact with porcine but not human endothelium leads to an endothelial calcium transient mediated via a G-protein-coupled receptor (GPCR) that results in up-regulation of porcine VCAM-1 and E-selectin. Although human monocyte adhesion was greater to porcine than to human endothelium, especially when studied under laminar flow, blockade of the xeno-specific endothelial calcium signals did not reduce adhesion of human monocytes to porcine endothelium. Human monocyte contact to porcine endothelium also resulted in reorganization of the F-actin cytoskeleton with a concomitant increase in endothelial monolayer permeability. In contrast to the effect on adhesion, these changes appear to be regulated through endothelial calcium signals. Taken together, these data suggest that human monocytes are capable of activating xenogeneic endothelial cells through calcium transients, as well as other distinct pathways. [source] The anti-inflammatory actions of methotrexate are critically dependent upon the production of reactive oxygen speciesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2003Darren C Phillips The mechanism of action by which methotrexate (MTX) exerts its anti-inflammatory and immunosuppressive effects remains unclear. The aim of this study is to investigate the hypothesis that MTX exerts these effects via the production of reactive oxygen species (ROS). Addition of MTX (100 nM,10 ,M) to U937 monocytes induced a time and dose dependent increase in cytosolic peroxide [peroxide]cyt from 6,16 h. MTX also caused corresponding monocyte growth arrest, which was inhibited (P<0.05) by pre-treatment with N-acetylcysteine (NAC; 10 mM) or glutathione (GSH; 10 mM). In contrast, MTX induction of [peroxide]cyt in Jurkat T cells was more rapid (4 h; P<0.05), but was associated with significant apoptosis at 16 h at all doses tested (P<0.05) and was significantly inhibited by NAC or GSH (P<0.05). MTX treatment of monocytes (10 nM,10 ,M) for 16 h significantly reduced total GSH levels (P<0.05) independently of dose (P>0.05). However, in T-cells, GSH levels were significantly elevated following 30 nM MTX treatment (P<0.05) but reduced by doses exceeding 1 ,M compared to controls (P<0.05). MTX treatment significantly reduced monocyte adhesion to 5 h and 24 h LPS (1 ,g ml,1) activated human umbilical vein endothelial cells (HUVEC; P<0.05) but not to resting HUVEC. Pre-treatment with GSH prevented MTX-induced reduction in adhesion. In conclusion, ROS generation by MTX is important for cytostasis in monocytes and cytotoxicity T-cells. Furthermore, MTX caused a reduction in monocyte adhesion to endothelial cells, where the mechanism of MTX action requires the production of ROS. Therefore its clinical efficacy can be attributed to multiple targets. British Journal of Pharmacology (2003) 138, 501,511. doi:10.1038/sj.bjp.0705054 [source] | |||||||||||||