title: Charge-dependent binding of granzyme A (MTSP-1) to basement membranes.
abstract: The murine T cell-associated serine proteinase granzyme A [also termed Murine T cell-associated serine proteinase-1 (MTSP-1), or SE-1] expresses optimal enzymatic activity under extracellular milieu conditions. It degrades a variety of proteins that are constituents of basement membranes. Granzyme A is harbored within intracellular storage granules from which its release can be induced by appropriate ligand binding to extracellular matrix receptors of T cells. Secreted granzyme A has, therefore, been implicated in the degradation of extracellular matrix barriers during T cell migration. Here we show that granzyme A binds to natural basement membranes in a charge-dependent manner. Binding of granzyme A to charged surfaces protects if from inhibition by natural high molecular weight inhibitors. The interaction of granzyme A with in vitro-produced extracellular matrices liberates basic fibroblast growth factor, which is bound to negatively charged heparan sulfate glycosaminoglycans of the extracellular matrix. We propose that the charge-dependent interaction of granzyme A with basement membranes has multiple, biologically relevant consequences.
authors.affiliation: Institut für Immunologie der Universität, Laboratorium für Immunpathologie, Heidelberg, FRG.
authors.forename: U
authors.initials: U
authors.lastname: Vettel
authors.forename: G
authors.initials: G
authors.lastname: Brunner
authors.forename: R
authors.initials: R
authors.lastname: Bar-Shavit
authors.forename: I
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: M D
authors.initials: MD
authors.lastname: Kramer
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D053804:Granzymes; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology*
chemical_list: D006025:Glycosaminoglycans; D016222:Fibroblast Growth Factor 2; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human