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 expre ss alpha4 and alpha5 but not alpha6 integrins of the beta1 family, and CD4(+) human blood T cells bind vasoactive intestinal peptide (VIP) w ith 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 mon oclonal antibodies to beta1 > alpha4 >> alpha5, but not to alpha6. Ant ibodies to beta1 and alpha4 suppressed to a similarly significant exte nt VIP stimulation of both MMP-dependent T cell chemotaxis through fib ronectin-enriched Matrigel and T cell degradation of H-3-type IV colla gen in the Matrigel, without affecting VIP-evoked secretion of MMP by suspensions of T cells. The lesser inhibition of VIP-enhanced adherenc e of T cells to fibronectin by anti-alpha5 antibody, than antibodies t o beta1 or alpha4 chains, was associated with lesser or no suppression of MMP-dependent T cell chemotaxis through Matrigel and T cell degrad ation 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 extravascu lar tissues. (C) 1996 Wiley-Liss, Inc.