Thrombin-induced conversion of fibrinogen to fibrin results in rapid platelet trapping which is not dependent on platelet activation or GPIb.
Br J Pharmacol
; 138(4): 574-83, 2003 Feb.
Article
en En
| MEDLINE
| ID: mdl-12598411
1. Activation of human platelets by thrombin is mediated by the proteolytic cleavage of two G-protein coupled protease-activated receptors, PAR-1 and PAR-4. However, thrombin also binds specifically to the platelet surface glycoprotein GPIb. It has been claimed that thrombin can induce aggregation of platelets via a novel GPIb-mediated pathway, which is independent of PAR activation and fibrinogen binding to alpha(IIb)beta(3) integrin, but dependent upon polymerizing fibrin and the generation of intracellular signals. 2. In the presence of both fibrinogen and the alpha(IIb)beta(3) receptor antagonist lotrafiban, thrombin induced a biphasic platelet aggregation response. The initial primary response was small but consistent and associated with the release of platelet granules. The delayed secondary response was more substantial and was abolished by the fibrin polymerization blocking peptide GPRP. 3. Cleavage of the extracellular portion of GPIb by mocarhagin partially inhibited thrombin-induced alpha(IIb)beta(3)-dependent aggregation and release, but had no effect on the secondary fibrin-dependent response. 4. Fixing of the platelets abolished alpha(IIb)beta(3)-dependent aggregation and release of adenine nucleotides, whereas the fibrin-dependent response remained, indicating that platelet activation and intracellular signalling are not necessary for this secondary 'aggregation'. 5. In conclusion, the secondary fibrin-dependent 'aggregation' response observed in the presence of fibrinogen and lotrafiban is a platelet trapping phenomenon dependent primarily on the conversion of soluble fibrinogen to polymerizing fibrin by thrombin.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibrinógeno
/
Fibrina
/
Trombina
/
Activación Plaquetaria
/
Agregación Plaquetaria
/
Complejo GPIb-IX de Glicoproteína Plaquetaria
Límite:
Humans
Idioma:
En
Revista:
Br J Pharmacol
Año:
2003
Tipo del documento:
Article
Pais de publicación:
Reino Unido