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Monocyte Recruitment (monocyte + recruitment)
Selected AbstractsRole of ,4,1 Integrins in Chemokine-Induced Monocyte Arrest under Conditions of Shear StressMICROCIRCULATION, Issue 1 2009SHARON J. HYDUK ABSTRACT Monocyte recruitment or emigration to tissues is an essential component of host defense in both acute and chronic inflammatory responses. Sequential molecular interactions mediate a cascade of tethering, rolling, arrest, stable adhesion, and intravascular crawling that culminates in monocyte diapedesis across the vascular endothelium and migration through the basement membrane of postcapillary venules. Integrins are complex adhesion and signaling molecules. Dynamic alterations in their conformation and distribution on the monocyte cell surface are required for many steps of monocyte emigration. Intracellular signaling initiated by chemokine receptors induces conformational changes in integrins that upregulate their affinity for ligands, and this is essential for monocyte arrest. This review focuses on the activation of monocyte ,4,1 integrins by endothelial chemokines, which is required for the arrest of monocytes rolling on vascular cell adhesion molecule 1 under shear flow. Using soluble ligand-binding assays and adhesion assays in parallel-plate flow chambers, critical signaling mediators in chemokine-induced ,4,1 integrin affinity upregulation and monocyte arrest have been identified, including phospholipase C, calcium, and calmodulin. [source] The combination of polymorphisms within MCP-1 and IL-1, associated with ulcerative colitisINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2009K.-S. Li Summary Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment to sites of inflammation. Raised level of MCP-1 has been widely demonstrated in the intestinal mucosa of patients with ulcerative colitis (UC), suggesting an important role of MCP-1 in the pathogenesis of UC. The ,2518A/G polymorphism in the promoter region of MCP-1 gene affecting its transcriptional activation has been reported recently. In order to assess the potential role of this polymorphism in UC, we examined its distribution in 162 unrelated UC patients and 203 healthy controls. In addition, considering the gene regulatory association between interleukin-1, (IL-1,) and MCP-1, we further examined whether the gene polymorphisms between MCP-1 and IL-1, exert synergetic effects on risk of UC. Our results show that the distribution of MCP-1 genotype or allele frequencies between UC patients and controls was not significantly different; however, the association between the polymorphism of MCP-1 ,2518 GG and the polymorphism of IL-1,,511 T in UC patients is significant (OR 2.062, 95% CI 1.034,4.113, P = 0.038). This is the first report describing the association between MCP-1 polymorphism and UC, and our data suggest that the MCP-1 ,2518 polymorphism itself does not represent an independent genetic risk factor for UC. In contrast, the combination polymorphisms between MCP-1 and IL-1, can increase UC risk significantly, which might help us understand the molecular mechanism underlying the development of UC. [source] Enhanced monocyte migration and pro-inflammatory cytokine production by Porphyromonas gingivalis infectionJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2010A. Pollreisz Pollreisz A, Huang Y, Roth GA, Cheng B, Kebschull M, Papapanou PN, Schmidt AM, Lalla E. Enhanced monocyte migration and pro-inflammatory cytokine production by Porphyromonas gingivalis infection. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01225.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective:,Porphyromonas gingivalis, a major periodontal pathogen, has been reported to be involved in atherogenesis. In order to further understand this pathogen's link with systemic inflammation and vascular disease, we investigated its influence on murine monocytes and macrophages from three different sources. Material and Methods:, Concanavalin A-elicited peritoneal macrophages, peripheral blood monocyte-derived macrophages and WEHI 274.1 monocytes were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. Results:, Infection with P. gingivalis 381 markedly induced monocyte migration and significantly enhanced production of the pro-inflammatory cytokines, tumor necrosis factor-, and interleukin-6. Consistent with a role for this pathogen's major fimbriae and/or its invasive capacity, infection with DPG3 had a minimal effect on both monocyte attraction and pro-inflammatory cytokine production. Conclusion:, Since monocyte recruitment and activation are important steps in the development of vascular inflammation and atherosclerosis, these results suggest that P. gingivalis infection may be involved in these processes. [source] Chemokine receptor CCR2 undergoes transportin1-dependent nuclear translocationPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 21 2008Nicolas Favre Abstract Chemokines (CCs) are small chemoattractant cytokines involved in a wide variety of biological and pathological processes. Released by cells in the milieu, and extracellular matrix and activating signalling cascades upon binding to specific G protein-coupled receptors (GPCRs), they trigger many cellular events. In various pathologies, CCs are directly responsible for excessive recruitment of leukocytes to inflammatory sites and recent studies using chemokine receptor (CCR) antagonists permitted these molecules to reach the market for medical use. While interaction of CCs with their receptors has been extensively documented, downstream GPCR signalling cascades triggered by CC are less well understood. Given the pivotal role of chemokine receptor 2 (CCR2) in monocyte recruitment, activation and differentiation and its implication in several autoimmune-inflammatory pathologies, we searched for potential new CCR2-interacting proteins by engineering a modified CCR2 that we used as bait. Herein, we show the direct interaction of CCR2 with transportin1 (TRN1), which we demonstrate is followed by CCR2 receptor internalization. Further characterization of this novel interaction revealed that TRN1-binding to CCR2 increased upon time in agonist treated cells and promotes its nuclear translocation in a TRN1-dependent manner. Finally, we provide evidence that following translocation, the receptor localizes at the outer edge of the nuclear envelope where it is finally released from TRN1. [source] CCR2 Regulates Monocyte Recruitment As Well As CD4+ Th1 Allorecognition After Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010A. E. Gelman Graft rejection remains a formidable problem contributing to poor outcomes after lung transplantation. Blocking chemokine pathways have yielded promising results in some organ transplant systems. Previous clinical studies have demonstrated upregulation of CCR2 ligands following lung transplantation. Moreover, lung injury is attenuated in CCR2-deficient mice in several inflammatory models. In this study, we examined the role of CCR2 in monocyte recruitment and alloimmune responses in a mouse model of vascularized orthotopic lung transplantation. The CCR2 ligand MCP-1 is upregulated in serum and allografts following lung transplantation. CCR2 is critical for the mobilization of monocytes from the bone marrow into the bloodstream and for the accumulation of CD11c+ cells within lung allografts. A portion of graft-infiltrating recipient CD11c+ cells expresses both recipient and donor MHC molecules. Two-photon imaging demonstrates that recipient CD11c+ cells are associated with recipient T cells within the graft. While recipient CCR2 deficiency does not prevent acute lung rejection and is associated with increased graft infiltration by T cells, it significantly reduces CD4+ Th1 indirect and direct allorecognition. Thus, CCR2 may be a potential target to attenuate alloimmune responses after lung transplantation. [source] Omega-3 polyunsaturated fatty acids ameliorate the severity of ileitis in the senescence accelerated mice (SAM)P1/Yit mice modelCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009H. Matsunaga Summary Clinical studies using omega-3 polyunsaturated fatty acids (,3-PUFA) to Crohn's disease (CD) are conflicting. Beneficial effects of dietary ,3-PUFA intake in various experimental inflammatory bowel disease (IBD) models have been reported. However, animal models of large intestinal inflammation have been used in all previous studies, and the effect of ,3 fat in an animal model of small intestinal inflammation has not been reported. We hypothesized that the effects of ,3 fat are different between large and small intestine. The aim of this study was to determine whether the direct effect of ,3 fat is beneficial for small intestinal inflammation. Senescence accelerated mice (SAM)P1/Yit mice showed remarkable inflammation of the terminal ileum spontaneously. The numbers of F4/80-positive monocyte,macrophage cells as well as ,7-integrin-positive lymphocytes in the intestinal mucosa were increased significantly compared with those in the control mice (AKR-J mice). The area of mucosal addressin cell adhesion molecule-1 (MAdCAM-1)-positive vessels was also increased. The degree of expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6 and interferon (IFN)-, mRNA were increased significantly compared with those in the control mice. The feeding of two different kinds of ,3 fat (fish-oil-rich and perilla-oil-rich diets) for 16 weeks to SAMP1/Yit mice ameliorated inflammation of the terminal ileum significantly. In both the ,3-fat-rich diet groups, enhanced infiltration of F4/80-positive monocytes/macrophages in intestinal mucosa of SAMP1/Yit mice cells and the increased levels of MCP-1, IL-6 and IFN-, mRNA expression were ameliorated significantly compared with those in the control diet group. The results suggest that ,3 fat is beneficial for small intestinal inflammation by inhibition of monocyte recruitment to inflamed intestinal mucosa. [source] | ||||||||||