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 major basal 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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Base Sequence
-
Basement Membrane / immunology
-
Blotting, Western
-
Cell Movement / immunology*
-
Cells, Cultured
-
Collagenases / biosynthesis
-
Collagenases / immunology*
-
Dipeptides / pharmacology
-
Flow Cytometry
-
Gelatinases / antagonists & inhibitors
-
Gelatinases / biosynthesis
-
Gelatinases / immunology*
-
Humans
-
Immunoenzyme Techniques
-
Matrix Metalloproteinase 2
-
Matrix Metalloproteinase 9
-
Matrix Metalloproteinase Inhibitors
-
Metalloendopeptidases / antagonists & inhibitors
-
Metalloendopeptidases / biosynthesis
-
Metalloendopeptidases / immunology*
-
Molecular Sequence Data
-
T-Lymphocytes / enzymology*
Substances
-
Dipeptides
-
Matrix Metalloproteinase Inhibitors
-
N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
-
Collagenases
-
Gelatinases
-
Metalloendopeptidases
-
Matrix Metalloproteinase 2
-
Matrix Metalloproteinase 9