Thromb Haemost 1995; 73(04): 693-701
DOI: 10.1055/s-0038-1653843
Original Articles
Platelets
Schattauer GmbH Stuttgart

Exposure of Human Platelets to Plasmin Results in the Expression of Irreversibly Active Fibrinogen Receptors

Samia Rabhi-Sabile
Inserm U.353, Hôpital Saint-Louis, Paris, France
,
Dominique Pidard
Inserm U.353, Hôpital Saint-Louis, Paris, France
› Author Affiliations
Further Information

Publication History

Received 31 August 1994

Accepted after resubmission 10 January 1995

Publication Date:
09 July 2018 (online)

Summary

Although plasmin can trigger strong platelet responses such as shape change and exocytosis of internal granules, limited platelet aggregation is induced by this proteinase, owing to its capacity to rapidly proteolyse secreted adhesive proteins. In this context, we have investigated the state of activation of the fibrinogen receptor, the integrin αIIbβ3, on platelets exposed to plasmin. Following incubation with plasmin at 37 °C, washing, and resuspension, platelets exhibit a moderate, low-velocity aggregation when stirred in the presence of fibrinogen. Optimum aggregability is observed when platelets have been exposed to plasmin activity of ≈0.5 CU/ml for 20 min, and aggregation is insensitive to the presence of antagonists such as prostaglandin (PG) E1 and apyrase. Plasmin-induced platelet aggregability is associated with the expression of active fibrinogen receptors on the cell surface, which, using a l25I-fibrinogen binding assay, can be quantified to ≈2,300 molecules per platelet. Exposure of active αIIbβ3 receptors appears to depend partially, but not totally on a metabolic activation and granule exocytosis at the time of incubation with plasmin. In contrast with a-thrombin, plasmin-induced activation of αIIbβ3 is sustained and cannot be reversed by exposure of platelets to PGE1. Immunoblotting analysis of the receptor subunits shows no extensive proteolytic modification of αIIbβ3 by plasmin, and only reveals a limited proteolysis of the aminoterminal domain of the αIIb subunit. In addition to their capacity to aggregate in the presence of fibrinogen alone, plasmin-treated platelets also show a potentiated aggregability in response to low doses of ADP. Thus, plasmin has the potential to activate the platelet fibrinogen receptor in such a way that it remains irreversibly available to fibrinogen on the surface of nonaggregated cells, a feature that may participate to pathological states of in vivo platelet hyperaggregability.

 
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