Integrin-dependent role of human T cell matrix metalloproteinase activity in chemotaxis through a model basement membrane

Human T lymphoblastoma cells of the CD4⁺ 8⁺ Tsup-1 line, that express alpha4 and alpha5 but not alpha6 integrins of the beta1 family, and CD4⁺ human blood T cells bind vasoactive intestinal peptide (VIP) with high affinity, leading to increased adherence, secretion of matrix metalloproteinases (MMPs), and chemotaxis. VIP-enhanced adherence of T cells to fibronectin was inhibited significantly by neutralizing monoclonal antibodies to beta1 > alpha4 >> alpha5, but not to alpha6. Antibodies to beta1 and alpha4 suppressed to a similarly significant extent VIP stimulation of both MMP-dependent T cell chemotaxis through fibronectin-enriched Matrigel and T cell degradation of ³H-type IV collagen in the Matrigel, without affecting VIP-evoked secretion of MMP by suspensions of T cells. The lesser inhibition of VIP-enhanced adherence of T cells to fibronectin by anti-alpha5 antibody, than antibodies to beta1 or alpha4 chains, was associated with lesser or no suppression of MMP-dependent T cell chemotaxis through Matrigel and T cell degradation of type IV collagen in the Matrigel in response to VIP. Specific beta1 integrins thus mediate interactions of stimulated T cells with basement membranes, including adherence, localized digestion by MMPs, and chemotactic passage, that promote entry of T cells into extravascular tissues. © 1996 Wiley-Liss, Inc.