Importance of fibrinogen and platelet membrane glycoprotein IIb/IIIa in shear-induced platelet aggregation.
The mechanism of shear-induced platelet aggregation was investigated using a polycarbonate cone and plate viscometer. After exposed to shear stress of 54-90 dyne/cm2 for 2 min. at 37 degrees C, platelets aggregated without a significant amount of serotonin release and lactic dehydrogenase leakage from platelets. Under this conditions, platelets from 2 patients with thrombasthenia and a patient with congenital afibrinogenemia failed to aggregate. When fibrinogen was added to platelet rich plasma from a patient with afibrinogenemia, shear-induced platelet aggregation occurred at the same extent of aggregation as observed in normal platelets. Shear-induced platelet aggregation was inhibited by monoclonal antibody to GPIIb/IIIa (1 microgram/ml) and synthetic peptide, Arg-Gly-Asp-Ser (RGDS) (1 mM). Apyrase and hirudin showed no effect on this aggregation. Indomethacin (100 microM) and thromboxane A2 synthetase inhibitor, OKY-046 (100 microM) markedly inhibited aggregation, while thromboxane A2 competitive inhibitor, ONO-3708 (100 microM) exhibited only partial inhibition. These results indicate that fibrinogen and GPIIb/IIIa are important for shear-induced platelet aggregation and that the induction of fibrinogen receptor on GPIIb/IIIa may partially depend upon thromboxane A2 synthesis in platelets.
Ikeda
Y
Y
Department of Haematology, School of Medicine, Keio University, Tokyo, Japan.
Murata
M
M
Araki
Y
Y
Watanabe
K
K
Ando
Y
Y
Itagaki
I
I
Mori
Y
Y
Ichitani
M
M
Sakai
K
K
D000347:Afibrinogenemia / Q000097:blood / Q000151:congenital; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D005340:Fibrinogen / Q000494:pharmacology*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010976:Platelet Count / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000494:pharmacology*; D013314:Stress, Mechanical; D013915:Thrombasthenia / Q000097:blood
D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen