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Stromal cells differentially regulate neutrophil and lymphocyte recruitment through the endothelium

McGettrick, Helen M. and Buckley, Christopher D. and Filer, Andrew and Ed Rainger, G. and Nash, Gerard B. (2010) Stromal cells differentially regulate neutrophil and lymphocyte recruitment through the endothelium. Immunology. no. ISSN 13652567

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URL of Published Version: http://dx.doi.org/10.1111/j.1365-2567.2010.03307.x

Identification Number/DOI: doi:10.1111/j.1365-2567.2010.03307.x

Stromal fibroblasts modify the initial recruitment of leucocytes by endothelial cells (EC), but their effects on subsequent transendothelial migration remain unclear. Here, EC and dermal or synovial fibroblasts were cultured on opposite surfaces of 3-lm pore filters and incorporated in static or flow-based migration assays. Fibroblasts had little effect on tumour necrosis factor-a-induced transendothelial migration of neutrophils,but tended to increase the efficiency of migration away from the endothelium.Surprisingly, similar close contact between EC and fibroblasts strongly reduced lymphocyte migration in static assays, and nearly abolished stable lymphocyte adhesion from flow. Fibroblasts did not alter endothelial surface expression of adhesion molecules or messenger RNA for chemokines. Inhibition of attachment did not occur when EC-fibroblast contact was restricted by using 04-lm pore filters, but under these conditions pre-treatment with heparinase partially inhibited adhesion. In the 3-lm pore co-cultures, inhibition of metalloproteinase activity partially recovered lymphocyte adhesion, but addition of CXCL12 (SDF-1a) to the endothelial surface did not. Hence, the ability of EC to present activating chemokines for lymphocytes may have been enzymatically inhibited by direct contact with fibroblasts. To avoid contact, we cultured EC and fibroblasts on separate 3-lm pore filters one above the other. Here,fibroblasts promoted the transendothelial migration of lymphocytes. Fibroblasts generate CXCL12, but blockade of CXCL12 receptor had no effect on lymphocyte migration. While stromal cells can provide signal(s)promoting leucocyte migration away from the sub-endothelial space,direct cell contact (which might occur in damaged tissue) may cause disruption of chemokine signalling, specifically inhibiting lymphocyte rather than neutrophil recruitment.

Type of Work:Article
Date:2010 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:Centre for Immune Regulation
Subjects:R Medicine (General)
Institution:University of Birmingham
Copyright Holders:Blackwell Publishing
ID Code:421
Refereed:YES
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