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 beta 3 integrin, the receptor for plasma fibrinogen. We have evaluated how the biological activities of these receptors can be potentially modulated through limited proteolysis 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 beta 3 integrin through intracellular metabolic pathways, but has no direct proteolytic activity on the receptor subunits. By contrast, EL does not activate the platelet metabolism, but specifically cleaves a short peptide sequence within the alpha IIb subunit, and this cleavage occurs in parallel 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 GPIb alpha subunit of the GPIb-IX receptor, eliminating the binding site for von Willebrand factor and diminishing the capacity of platelets to interact with this adhesion protein. Thus, neutrophil proteinases have the potential to regulate the activity of platelet adhesion receptors, and such experimental observations may prove to be relevant in vivo in various pathological conditions.
Pidard
D
D
INSERM U 353, Hôpital Saint-Louis, Paris, France.
Renesto
P
P
Rabhi
S
S
Chignard
M
M
D010450:Endopeptidases / Q000097:blood*; D006801:Humans; D016023:Integrins / Q000737:chemistry* / Q000502:physiology; D007962:Leukocytes / Q000201:enzymology*; D010973:Platelet Adhesiveness / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000502:physiology; D013329:Structure-Activity Relationship
D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C028254:von Willebrand factor receptor; D010450:Endopeptidases