REGULATION OF THE STRUCTURE AND ACTIVITY OF PLATELET-ADHESION RECEPTORS BY LEUKOCYTE PROTEINASES

Two major membrane receptors implicated in the adhesive properties of blood platelets are the GPIb-IX complex, a receptor for subendothelial von Willebrand factor, and the alpha(IIb)beta3 integrin, the receptor for plasma fibrinogen. We have evaluated how the biological activitie s of these receptors can be potentially modulated th rough limited pro teolysis when platelets are exposed to the serine-proteinases secreted by activated polymorphonuclear neutrophils, i.e., leukocyte elastase (EL) and cathepsin G (CG). CG can activate the alpha(IIb)beta3 integri n through intracellular metabolic pathways, but has no direct proteoly tic activity on the receptor subunits. By contrast, EL does not activa te the platelet metabolism, but specifically cleaves a short peptide s equence within the alpha(IIb) subunit, and this cleavage occurs in par allel with an up-regulation of the activity of the fibrinogen receptor . On another hand, both EL and CG cleave the amino-terminal portion of the GPIbalpha subunit of the GPIb-IX receptor, eliminating the bindin g site for von Willebrand factor and diminishing the capacity of plate lets to interact with this adhesion protein. Thus, neutrophil proteina ses have the potential to regulate the activity of platelet adhesion r eceptors, and such experimental observations may prove to be relevant in vivo in various pathological conditions.