Integrin alpha1beta1 (VLA-1) mediates adhesion of activated intraepithelial lymphocytes to collagen.
Intraepithelial lymphocytes (IELs) from human intestinal epithelium are memory CD8+ T cells that bind to epithelial cells through human mycosal lymphocyte (HML)-1 and to mesenchymal cells through very late activation antigen-4 (VLA-4). Their binding of extracellular matrix proteins and the mechanism involved were tested. Activated 51Cr-labelled lymphocytes were incubated in protein-coated microwells with various additives. After washing, the adherent cells were detected by radioactivity. The percentages of activated IELs that bound to collagen types I and IV were 20 and 31%, respectively; fewer bound to fibronectin or laminin. Compared to interleukin-2-activated peripheral blood CD8+ T lymphocytes, more IELs bound collagen IV and fewer bound fibronectin. IEL adhesion to collagen (but not fibronectin or laminin) was up-regulated by antibody ligation of CD2 or by protein kinase C stimulation by phorbol ester; staurosporine reduced binding, while herbimycin, phytohaemagglutinin and CD3 ligation had no effect. Antibody-blocking of integrin VLA-1 subunits alpha1 (CD49a) and beta1 (CD18) inhibited adhesion to collagen type I by 82+/-6% and to type IV by 94+/-1% (P<0.001), implicating VLA-1 as the main collagen receptor for IELs. Cell adhesion was dependent on extracellular divalent cations, a characteristic event of VLA-1 never before shown for IELs: manganese and magnesium ions supported binding in a dose-dependent manner; calcium ions inhibited their effectiveness. Therefore, IELs bind collagen through integrin alpha1beta1 after protein kinase C activation. Adhesion is modulated by divalent cations.
Roberts
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AI
Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NY, USA.
Brolin
R E
RE
Ebert
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EC
D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D018929:Cell Culture Techniques; D003094:Collagen / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D039222:Integrin alpha1beta1; D016023:Integrins / Q000378:metabolism*; D007376:Interleukin-2 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D039222:Integrin alpha1beta1; D016023:Integrins; D007376:Interleukin-2; D003094:Collagen; D011493:Protein Kinase C