Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.
We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.
Selheim
F
F
Department of Biochemistry and Molecular Biology, University of Bergen, Norway. frode.selheim@pki.uib.no
Holmsen
H
H
Vassbotn
F S
FS
D015703:Antigens, CD / Q000032:analysis; D000954:Antigens, Surface / Q000097:blood; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005434:Flow Cytometry; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D060149:Tetraspanin 30
D015703:Antigens, CD; D000954:Antigens, Surface; C554586:CD63 protein, human; D005343:Fibrinolytic Agents; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D060149:Tetraspanin 30; D006493:Heparin