Differential induction of gelatinase B (MMP-9) and gelatinase A (MMP-2) inT lymphocytes upon alpha(4)beta(1-)mediated adhesion to VCAM-1 and the CS-1 peptide of fibronectin

Integrin alpha(4)beta(1) on the surface of T lymphocytes interacts with vas cular cell adhesion molecule-1 (VCAM-1) and fibronectin during migration of lymphocytes from the blood to sites of inflammation. Migrating lymphocytes actively modify their environment through a number of mechanisms including proteolysis of the extracellular matrix by matrix metalloproteinases (MMP) synthesized by the cells. In this study, expression of MMP upon alpha(4)be ta(1)-mediated adhesion of leukocytes to two major ligands, the IIICS-1 dom ain of fibronectin and VCAM-1, has been examined. Adhesion of T lymphoblast oid Jurkat cells to the CS-l peptide induced expression of mRNA for two MMP s, gelatinase A (MMP-2) and gelatinase B (MMP-9). As evaluated by relative RT-PCR and Northern blot analyses, the level of mRNA was upregulated about 4- to B-fold for both MMPs compared to control cells maintained in suspensi on. With time, both enzymes were detected in conditioned media and inside t he cells, and their identities were verified by Western blotting and gelati n zymography, Adhesion of Jurkat cells to the second major alpha(4)beta(1) ligand, VCAM-1, upregulated mRNA for MMP-2 (3.5-fold) and failed to induce expression of mRNA for MMP-9. Accordingly, only MMP-2 protein was detected in conditioned media of cells adherent to VCAM-1. Occupancy of alpha(4)beta (1) on the surface of suspended cells with soluble CS-l peptide or VCAM-1 d id not upregulate synthesis and release of MMPs. A similar pattern of induc tion of MMPs after adhesion to CS-1 and VCAM-1 was observed in T lymphocyte s isolated from human blood. These results demonstrate that adhesion of T l ymphocytes through alpha(4)beta(1) to different ligands, which bind to simi lar or overlapping sites in the integrin, induces intracellular events lead ing to distinct patterns of MMPs biosynthesis. (C) 2000 Academic Press.