Differential induction of gelatinase B (MMP-9) and gelatinase A (MMP-2) in T lymphocytes upon α4β1-mediated adhesion to VCAM-1 and the CS-1 peptide of fibronectin

Valentin P. Yakubenko, Roy R. Lobb, Edward F. Plow, Tatiana P. Ugarova

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Integrin α4β1 on the surface of T lymphocytes interacts with vascular 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 α4β1-mediated adhesion of leukocytes to two major ligands, the IIICS-1 domain of fibronectin and VCAM-1, has been examined. Adhesion of T lymphoblastoid Jurkat cells to the CS-1 peptide induced expression of mRNA for two MMPs, 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 5-fold for both MMPs compared to control cells maintained in suspension. With time, both enzymes were detected in conditioned media and inside the cells, and their identities were verified by Western blotting and gelatin zymography. Adhesion of Jurkat cells to the second major α4β1 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 α4β1 on the surface of suspended cells with soluble CS-1 peptide or VCAM-1 did not upregulate synthesis and release of MMPs. A similar pattern of induction of MMPs after adhesion to CS-1 and VCAM-1 was observed in T lymphocytes isolated from human blood. These results demonstrate that adhesion of T lymphocytes through α4β1 to different ligands, which bind to similar or overlapping sites in the integrin, induces intracellular events leading to distinct patterns of MMPs biosynthesis. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)73-84
Number of pages12
JournalExperimental Cell Research
Volume260
Issue number1
DOIs
StatePublished - Oct 10 2000
Externally publishedYes

Keywords

  • Adhesion
  • Fibronectin
  • Leukocytes
  • MMP
  • VCAM-1

ASJC Scopus subject areas

  • Cell Biology

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