Depending on the time of addition, prostaglandin I2 (PGI2; ≥10-9 M) either inhibits or reverses platelet agglutination mediated by human factor VIII-related von Willebrand factor activity (FVIII(vWF) and ristocetin, or bovine FVIII(vWF) alone. 6-keto-PGF(1α), the inactive metabolite of PGI2, is without effect. PGI2 inhibition is potentiated by the phosphodiesterase inhibitor, theophylline, and is not the result of PGI2 suppression of ADP release. PGI2 (±theophylline) does not inhibit ristocetin-induced binding of purified human 125I-FVIII(vWF) multimers to washed platelets or to platelets treated with PGI2 and then formalin fixed (although subsequent agglutination of these platelets is impaired). Washed platelets treated previously with 2-aminoethylisothiouronium bromide (AET), an agent that reduces disulfide bonds and alters platelet membranes, also bind human 125I-FVIII(vWF) multimers without agglutinating. We conclude that FVIII(vWF)-mediated agglutination requires both functional platelet FVIII(vWF) binding sites and platelet-platelet cohesion sites, and that platelet surface cohesion sites are altered by AET and PGI2. PGI2 from adjacent intact endothelial cells may prevent excessive platelet accumulation on exposed subendothelium without suppressing an essential hemostatic process- the binding of platelets to subendothelial FVIII(vWF).
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|State||Published - Jan 1 1981|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)