INTERACTION OF PLATELETS WITH DIFFERENT ISOTYPES OF HUMAN COLLAGEN: THE COLLAGEN-RECEPTOR AND SIGNAL-RES-P0NSE COUPLING:

Abstract

Platelet-collagen interaction is important in primary hemostasis and thrombosis. However, little is known about the interaction of platelets with genetically distinct collagen types I, III, IV, and V (Cl, ClII, CIV, CV) in their triple helical form. Here we report on the interaction of gel- filtered platelets with surfaces coated with monomeric collagen isotypes and the binding of 125-iodine-labeled Cl to platelets. It was shown that the binding of monomeric Cl is dose and time-dependent, saturable and specific, since it is competitively inhibited by unlabeled Cl, but not by unlabeled CV. Scatchard analysis reveals a receptor-class with a Kd of 2.5 x 10−8M. The result suggests that the different collagen isotypes may bind to platelets through various specific binding sites. Confirming that, we demonstrated, that interaction of platelets with collagen-coated surfaces is associated with the activation of different intra- and extracellular signal transduction systems: Initial attachment of discoid platelets to a CV-substrate does not induce neither synthesis of prostanoids nor changes of cyclic AMP-level. Adhesion and massive spreading of platelets on a CIV-substrate result in a decrease of stimulated cAMP-level without any synthesis of prostanoids. Only thrombus-formation during interaction of platelets with Cl- or CHI-coated surfaces is accompanied by a parallel decrease of cAMP and massive synthesis of platelet prostanoids. Additionally, it was shown that the stable prostacyclin analogue, carbacyc-lin, inhibited thrombus-formation and platelet spreading, whereas the PGH2/TXA2-receptor antagonists, 13-Azaprostanoic acid ana BM 13.177, completely inhibited thrombus-formation without any effect on platelet spreading.