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Lymphocyte Adhesion (lymphocyte + adhesion)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

The role of MAPK in governing lymphocyte adhesion to and migration across the microvasculature in inflammatory bowel disease

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2009
Franco Scaldaferri
Abstract Lymphocyte recruitment is a key pathogenic event in inflammatory bowel disease (IBD). Adhesion of T cells to human intestinal microvascular endothelial cells (HIMEC) is mediated by ICAM-1, VCAM-1 and fractalkine (FKN), but the signaling molecules that orchestrate this process have yet to be identified. Because MAPK play an important role in the response of many cell types to pro-inflammatory stimuli, we assessed the functional role of p38 MAPK, p42/44 MAPK and JNK in the regulation of lymphocyte adhesion to and chemotaxis across the microvasculature in IBD. We found that the MAPK were phosphorylated in the bowel microvasculature and human intestinal fibroblasts of patients with IBD but not of healthy individuals. Stimulation of HIMEC with TNF- , triggered phosphorylation of the MAPK, and up-regulation of VCAM-1, FKN and ICAM-1. Blockade of p38 decreased the expression of all MAPK by 50% (p<0.01), whereas inhibition of p42/44 decreased the expression of ICAM-1 and FKN by 50% (p<0.01). Treatment of human intestinal fibroblasts with TNF- , elicited production of IL-8 and MCP-1, which was reduced (p<0.05) by blockade of p38 and p42/44. Finally, blockade of p38 and p42/44 reduced lymphocyte adhesion to (p<0.05) and transmigration across (p<0.05) HIMEC monolayers. These findings suggest a critical role for MAPK in governing lymphocyte influx into the gut in IBD patients, and their blockade may offer a molecular target for blockade of leukocyte recruitment to the intestine. [source]

Antiangiogenic and Immunomodulatory Effects of Rapamycin on Islet Endothelium: Relevance for Islet Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2006
V. Cantaluppi
Donor intra-islet endothelial cells contribute to neovascularization after transplantation. Several factors may interfere with this process and ultimately influence islet engraftment. Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. The aim of this study was to evaluate the effects of rapamycin on islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from freshly purified human islets and the formation of capillary-like structures in vitro and in vivo after subcutaneous injection within Matrigel plugs into SCID mice. Rapamycin decreased migration, proliferation and angiogenic properties of human and mouse islet-derived endothelial cell lines with appearance of apoptosis. The expression of angionesis-related factors VEGF, ,V,3 integrin and thrombospondin-1 on islet endothelium was altered in the presence of rapamycin. On the other hand, rapamycin decreased the surface expression of molecules involved in immune processes such as ICAM-1 and CD40 and reduced the adhesion of T cells to islet endothelium. Our results suggest that rapamycin exerts dual effects on islet endothelium inducing a simultaneous inhibition of angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion and activation. [source]

Involvement of MAPKs and NF-,B in tumor necrosis factor ,,induced vascular cell adhesion molecule 1 expression in human rheumatoid arthritis synovial fibroblasts

ARTHRITIS & RHEUMATISM, Issue 1 2010
Shue-Fen Luo
Objective To investigate the roles of MAPKs and NF-,B in tumor necrosis factor , (TNF,),induced expression of vascular cell adhesion molecule 1 (VCAM-1) in human rheumatoid arthritis synovial fibroblasts (RASFs). Methods Human RASFs were isolated from synovial tissue obtained from patients with RA who underwent knee or hip surgery. The involvement of MAPKs and NF-,B in TNF,-induced VCAM-1 expression was investigated using pharmacologic inhibitors and transfection with short hairpin RNA (shRNA) and measured using Western blot, reverse transcriptase,polymerase chain reaction, and gene promoter assay. NF-,B translocation was determined by Western blot and immunofluorescence staining. The functional activity of VCAM-1 was evaluated by lymphocyte adhesion assay. Results TNF,-induced VCAM-1 expression, phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK, and translocation of NF-,B were attenuated by the inhibitors of MEK-1/2 (U0126), p38 (SB202190), JNK (SP600125), and NF-,B (helenalin) or by transfection with their respective shRNA. TNF,-stimulated translocation of NF-,B into the nucleus and NF-,B promoter activity were blocked by Bay11-7082, but not by U0126, SB202190, or SP600125. VCAM-1 promoter activity was enhanced by TNF, in RASFs transfected with VCAM-1-Luc, and this promoter activity was inhibited by Bay11-7082, U0126, SB202190, and SP600125. Moreover, up-regulation of VCAM-1 increased the adhesion of lymphocytes to the RASF monolayer, and this adhesion was attenuated by pretreatment with helenalin, U0126, SP600125, or SB202190 prior to exposure to TNF, or by anti,VCAM-1 antibody before the addition of lymphocytes. Conclusion In RASFs, TNF,-induced VCAM-1 expression is mediated through activation of the p42/p44 MAPK, p38 MAPK, JNK, and NF-,B pathways. These results provide new insights into the mechanisms underlying cytokine-initiated joint inflammation in RA and may inspire new targeted therapeutic approaches. [source]