Effects of C-reactive protein on platelet function. III. The role of cAMP, contractile elements, and prostaglandin metabolism in CRP-induced inhibition of platelet aggregation and secretion.
It was previously demonstrated that C-reactive protein (CRP) inhibits platelet aggregation and release reactions, activation of platelet factor 3, and platelet-dependent clot retraction. Multiple considerations including selective inhibition of secondary wave aggregation suggested that CRP exerted its inhibitory effects by interfering with the release of endogenous ADP. In the present investigation, CRP was found by direct assay to inhibit the release of endogenous ADP and/or serotonin concomitant with inhibition of platelet aggregation stimulated by ADP, epinephrine, thrombin, and AHGG. CRP did not induce an increase in the basal level of platelet cAMP, suggesting independence of a direct effect upon this mediator system. Furthermore, CRP did not inhibit the aggregation and secretion induced by the antibiotic ionophore A23187, suggesting the absence of a direct effect upon the activation of platelet contractile elements. By contrast, CRP did inhibit both thrombin-induced release of malondialdehyde, a prostaglandin endoperoxide nonprostanoate endproduct, and platelet aggregation induced by the prostaglandin endoperoxide precursor arachidonic acid. These data, therefore, raise the possibility that CRP inhibits platelet reactivities by interfering with an aspect of porstaglandin metabolism, and that this occurs subsequent to the hydrolytic accumulation of arachidonic acid and prior to the movement of calcium from the platelet dense tubules. These studies support the concept that CRP serves to modulate platelet reactivities during acute inflammatory reactions.
D000244:Adenosine Diphosphate / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology*; D002097:C-Reactive Protein / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D003609:Dactinomycin / Q000378:metabolism; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D010974:Platelet Aggregation; D011453:Prostaglandins / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
D001095:Arachidonic Acids; D011453:Prostaglandins; D003609:Dactinomycin; D012701:Serotonin; D008315:Malondialdehyde; D000244:Adenosine Diphosphate; D002097:C-Reactive Protein; D000242:Cyclic AMP