T cell gelatinases mediate basement membrane transmigration in vitro.
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.
Leppert
D
D
Department of Neurology, University of California at San Francisco 94143, USA.
Waubant
E
E
Galardy
R
R
Bunnett
N W
NW
Hauser
S L
SL
D001483:Base Sequence; D001485:Basement Membrane / Q000276:immunology; D015153:Blotting, Western; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis / Q000276:immunology*; D004151:Dipeptides / Q000494:pharmacology; D005434:Flow Cytometry; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000201:enzymology*
D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9