D. Pidard et al., REGULATION OF THE STRUCTURE AND ACTIVITY OF PLATELET-ADHESION RECEPTORS BY LEUKOCYTE PROTEINASES, Nouvelle revue francaise d'hematologie, 36, 1994, pp. 190000099-190000101
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.