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The Affinity of Integrin α4β1 Governs Lymphocyte Migration

2001; American Association of Immunologists; Volume: 167; Issue: 5 Linguagem: Inglês

10.4049/jimmunol.167.5.2824

1550-6606

David M. Rose, Valentin Grabovsky, R. Alon, Mark H. Ginsberg,

Monoclonal and Polyclonal Antibodies Research

Abstract The interaction of integrin α4β1 with endothelial VCAM-1 controls the trafficking of lymphocytes from blood into peripheral tissues. Cells actively regulate the affinity of α4β1 for VCAM-1 (activation). To investigate the biological function of α4β1 activation, we isolated Jurkat T cell lines with defective α4β1 activation. Using these cells, we found that α4β1-stimulated αLβ2-dependent cell migration was dramatically reduced in cells with defects in α4β1 activation. These cells required 20 times more VCAM-1 to promote αLβ2-dependent cell migration. This defect was at the level of α4β1 affinity as an activating α4β1 Ab rescued α4β1-stimulated αLβ2-dependent migration. In contrast, migration of α4β1 activation-defective cells on VCAM-1 alone was enhanced at higher VCAM-1 densities. Thus, α4β1 activation determines a set point or threshold at which VCAM-1 can regulate αLβ2-dependent as well as α4β1-dependent cell migration. Changes in this set point may specify preferred anatomical sites of integrin-dependent leukocyte emigration from the bloodstream.