Endocytosis of fibrinogen into megakaryocyte and platelet alpha-granules is mediated by alpha IIb beta 3 (glycoprotein IIb-IIIa)
Recently, we showed that platelet alpha-granule fibrinogen is derived entirely from endocytic uptake and not from megakaryocyte synthesis, as previously thought. In this present report, we identify the receptor that mediates endocytosis. We have found that barbourin, a unique disintegrin that is a specific antagonist of alpha IIb beta 3, inhibits the endocytic uptake of fibrinogen into alpha-granules. Continuous intravenous infusion of barbourin (200 micrograms/h) into guinea pigs blocked collagen-induced platelet aggregation as well as endocytosis of biotinylated fibrinogen into megakaryocytes; however, endocytosis of biotinylated albumin by megakaryocytes was not affected. Thus, we have shown that endocytosis of fibrinogen into megakaryocyte and platelet alpha-granules is receptor-mediated, and that alpha IIb beta 3 is the primary receptor.
Department of Pathology, University of California, San Francisco 94143-0506.
P
P
Handagama
R M
RM
Scarborough
M A
MA
Shuman
D F
DF
Bainton
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D003435:Crotalid Venoms / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D004705:Endocytosis; D005340:Fibrinogen / Q000378:metabolism*; D006168:Guinea Pigs; D008533:Megakaryocytes / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism
D003435:Crotalid Venoms; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C068858:barbourin; D005340:Fibrinogen