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Cell Chemoattractants (cell + chemoattractant)
Selected AbstractsMature antigen-experienced T helper cells synthesize and secrete the B cell chemoattractant CXCL13 in the inflammatory environment of the rheumatoid jointARTHRITIS & RHEUMATISM, Issue 11 2008Antonio Manzo Objective Synovial B cells play a critical role in rheumatoid arthritis (RA), being involved in autoantibody synthesis, T cell activation, and cytokine production. CXCL13 is a B cell chemoattractant that is instrumental in synovial B cell organization; the regulatory determinants of CXCL13 in inflammation are poorly characterized. This study was undertaken to investigate the functional involvement of synovial T cells in the ectopic expression of CXCL13 in RA. Methods CXCL13 production and regulation were addressed using immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, multicolor flow cytometry, and enzyme-linked immunosorbent assay, by in situ,ex vivo analysis and in vitro functional assays with rheumatoid synovial tissue and primary cells. Results CXCL13 messenger RNA and protein expression and spontaneous CXCL13 secretion were detected in RA synovial fluid T cells but were not detected (or were detected only occasionally) in peripheral blood T cells. Analysis of tissue expression confirmed cytoplasm localization of CXCL13 in T lymphocytes infiltrating B cell follicles and small perivascular aggregates. Multicolor characterizations in synovial fluid demonstrated CXCL13 expression in antigen-experienced T helper cells, frequently characterized by terminal differentiation and the lack of the follicular helper T cell markers CXCR5 and BCL6 protein. In vitro functional assays revealed the enhancing effect of T cell receptor,CD28 engagement on CXCL13 production and secretion in primary cells. Conclusion Our findings define a new functional property of synovial T cells, demonstrating their active involvement in the local production of B cell chemoattractants, and support a direct contribution of the adaptive immune system and antigen-dependent signals in the mechanisms of B cell localization in RA. [source] Chemokine and cytokine expression in murine intestinal epithelium following Nippostrongylus brasiliensis infectionPARASITE IMMUNOLOGY, Issue 2 2002Anne Rosbottom Summary Infection of mice with the nematode parasite Nippostrongylus brasiliensis results in a well characterized intestinal mastocytosis with intraepithelial migration of mucosal mast cells (MMC). The molecules mediating this response are unknown. We examined expression of several putative mast cell chemoattractants in intestinal epithelium following N. brasiliensis infection. Expression of the chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1,(MIP-1,), RANTES (regulated on activation normal T-cell expressed and secreted), fractalkine, and thymocyte expressed chemokine (TECK); and the cytokines stem cell factor (SCF) and transforming growth factor ,1 (TGF,1), was constitutive and no alteration was detected following infection. MCP-1 expression was also constitutive but at much lower levels and increased expression was detected on days 7 and 14 postinfection. Expression of MCP-1 in whole jejunum was at much higher levels than in epithelium. Constitutive expression of MCP-1, MIP-1, and TGF,1 was also detected in cultured bone marrow-derived homologues of MMC. In an intestinal epithelial cell line (CMT-93), there was constitutive expression of SCF, TGF,1, fractalkine and MCP-1. The results show that, in vivo, epithelium is a potentially important source of mast cell chemoattractants. [source] IL-6, but not IL-4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: involvement of both mitogen-activated protein kinases and phosphatidylinositol 3-kinase signalling pathwaysAPMIS, Issue 8 2009ANNA MISIAK-T, OCZEK Misiak-T,oczek A, Brzezi,ska-B,aszczyk E. IL-6, but not IL-4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: Involvement of both mitogen-activated protein kinases and phosphatidylinositol 3-kinase signalling pathways. APMIS 2009; 117: 558,67. An increase in the number of mast cells within tissues is observed in many pathophysiological conditions. Current data indicate that migration of mature mast cells might be one of the key mechanisms responsible for rapid local accumulation of these cells. Considering that interleukin (IL)-6 and IL-4, as well as tumour necrosis factor (TNF), influence mast cell activity in various ways, the purpose of the current study was to examine whether these cytokines function as rat peritoneal mast cell chemoattractants. We showed that IL-4, in the concentration range from 10,6 to 10,3 ng/ml, did not induce a mast cell migratory response, even in the presence of laminin and fibronectin. Under the same experimental conditions, mast cells were shown to migrate in response to IL-6 stimulation in the presence of laminin. The optimal concentration of IL-6 for maximal migration of mast cells was 10,4 ng/ml (i.e. ,5 nM). In comparison, the optimal concentration of TNF for maximal migration of mast cells was 5 × 10,5 ng/ml (i.e. ,3 fM). IL-6-stimulated mast cell migration was the result of chemokinesis, whereas TNF-induced migration was the result of chemotaxis. Mast cell migratory responses to IL-6 and TNF were entirely blocked by specific anti-IL-6R and anti-TNFR1 antibodies. We also documented that the migration response of mast cells to stimulation with IL-6 and TNF was mediated through signal transduction pathways involving mitogen-activated protein kinases and phosphatidylinositol 3-kinase. Taken together, our results indicate that IL-6, as well as TNF, induces tissue mast cell migration. Thus, these proinflammatory cytokines can be responsible for mast cell accumulation at the site of diverse conditions accompanied by inflammation. [source] Mature antigen-experienced T helper cells synthesize and secrete the B cell chemoattractant CXCL13 in the inflammatory environment of the rheumatoid jointARTHRITIS & RHEUMATISM, Issue 11 2008Antonio Manzo Objective Synovial B cells play a critical role in rheumatoid arthritis (RA), being involved in autoantibody synthesis, T cell activation, and cytokine production. CXCL13 is a B cell chemoattractant that is instrumental in synovial B cell organization; the regulatory determinants of CXCL13 in inflammation are poorly characterized. This study was undertaken to investigate the functional involvement of synovial T cells in the ectopic expression of CXCL13 in RA. Methods CXCL13 production and regulation were addressed using immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, multicolor flow cytometry, and enzyme-linked immunosorbent assay, by in situ,ex vivo analysis and in vitro functional assays with rheumatoid synovial tissue and primary cells. Results CXCL13 messenger RNA and protein expression and spontaneous CXCL13 secretion were detected in RA synovial fluid T cells but were not detected (or were detected only occasionally) in peripheral blood T cells. Analysis of tissue expression confirmed cytoplasm localization of CXCL13 in T lymphocytes infiltrating B cell follicles and small perivascular aggregates. Multicolor characterizations in synovial fluid demonstrated CXCL13 expression in antigen-experienced T helper cells, frequently characterized by terminal differentiation and the lack of the follicular helper T cell markers CXCR5 and BCL6 protein. In vitro functional assays revealed the enhancing effect of T cell receptor,CD28 engagement on CXCL13 production and secretion in primary cells. Conclusion Our findings define a new functional property of synovial T cells, demonstrating their active involvement in the local production of B cell chemoattractants, and support a direct contribution of the adaptive immune system and antigen-dependent signals in the mechanisms of B cell localization in RA. [source] | ||||||||||