Charge‐dependent binding of granzyme A (MTSP‐1) to basement membranes

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Abstract
The murine T cell-associated serine proteinase granzyme A [also termed Murine Tcell-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 Tcells. 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 it 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.

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