T cell gelatinases madiate basement membrane transmigration in vitro

D. Leppert, E. Waubant, R. Galardy, N. W. Bunnett, S. L. Hauser

Research output: Contribution to journalArticlepeer-review

Abstract

T cell homing into extravascular sites requires penetration across the subendothelial basal lamina, a specialized nonfibrillar connective tissue structure that anchors endothelial cells to parenchymal surfaces. Herein, we show that normal human T cells express gelatinases A and B, two matrix metalloproteinases active against the majorbasal lamina constituents, collagen types IV and V. Expression is confirmed at both the mRNA and protein levels. Gelatinase B is expressed constitutively, whereas gelatinases A and B expression is induced by T cell activation. In vitro migration of resting T cells across a basal lamina equivalent is mediated by gelatinase B, because it is specifically blocked by GM6001, a hydroxamic acid inhibitor of matrix metalloproteinases. Inhibition of T cell homing by interference with gelatinase function may represent a useful approach to the treatment of T cell-mediated autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)4379-4389
Number of pages11
JournalJournal of Immunology
Volume154
Issue number9
StatePublished - 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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