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© The Rockefeller University Press, 0021-9525/1997//1437 $5.00
The Journal of Cell Biology, Volume 138, Number 6, , 1997 1437-1447

Article

Integrin Cross Talk: Activation of Lymphocyte Function-associated Antigen-1 on Human T Cells Alters {alpha}4β1- and {alpha}5β1-mediated Function



Joanna C. Porter and Nancy Hogg

Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom

A regulated order of adhesion events directs leukocytes from the vascular compartment into injured tissues in response to inflammatory stimuli. We show that on human T cells, the interaction of the β2 integrin leucocyte function–associated antigen-1 (LFA-1) with its ligand intercellular adhesion molecule-1 (ICAM-1) will decrease adhesion mediated by {alpha}4β1 and, to a lesser extent, {alpha}5β1. Similar inhibition is also seen when T cells are exposed to mAb 24, which stabilizes LFA-1 in an active state after triggering integrin function through divalent cation Mg2+, PdBu, or T cell receptor/ CD3 complex (TCR/CD3) cross-linking. Such cross talk decreases {alpha}4β1 integrin–mediated binding of T cells to fibronectin and vascular cell adhesion molecule-1 (VCAM-1). In contrast, ligand occupancy or prolonged activation of β1 integrin has no effect on LFA-1 adhesion to ICAM-1. We also show that T cell migration across fibronectin, unlike adhesion, is mediated solely by {alpha}5β1, and is increased when the {alpha}4β1-mediated component of fibronectin adhesion is decreased either by cross talk or the use of {alpha}4-blocking mAb. The ability of mAb 24 Fab' fragments to induce cross talk without cross-linking LFA-1 suggests signal transduction through the active integrin. These data provide the first direct evidence for cross talk between LFA-1 and β1 integrins on T cells. Together, these findings imply that activation of LFA-1 on the extravasating T cell will decrease the binding to VCAM-1 while enhancing the subsequent migration on fibronectin. This sequence of events provides a further level of complexity to the coordination of T cell integrins, whose sequential but overlapping roles are essential for transmigration.

Abbreviations used in this paper: ICAM-1, intercellular adhesion molecule-1; LFA-1, lymphocyte function–associated antigen-1; PdBu, phorbol-12,13-dibutyrate; TCR/CD3, T cell receptor/CD3 complex; VCAM-1, vascular cell adhesion molecule-1.

Address all correspondence to J.C. Porter, Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom. Tel.: 44-171-269-3569; Fax: 44-171-269-3093; e-mail: porterj{at}europa.lif.icnet.uk


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