Cox-2 is not involved in thromboxane biosynthesis by activated human platelets

The occurrence of aspirin resistance has been inferred by the assessment of platelet aggregation ex vivo in patients with ischemic vascular syndromes taking aspirin. Since aspirin is a weak inhibitor of the inducible isoform of prostaglandin H synthase (COX-2), it was suggested that COX-2 may play a role in aspirin resistance. However the cellular source(s) of COX-2 possib ly responsible for aspirin resistance remains unknown. Recently, the expres sion of the inducible isoform of COX-2 in circulating human platelets was r eported. To investigate the possible contribution of COX-2 expression in pl atelet thromboxane (TX) biosynthesis, we have compared the inhibitory effec ts of NS-398 and aspirin, selective inhibitbrs of COX-2 and COX-I, respecti vely, on prostanoid biosynthesis by thrombin-stimulated platelets vs lipopo lysaccharide (LPS)-stimulated monocytes (expressing high levels of COX-2) i solated from whole blood of healthy subjects. NS-398 was 180-fold more pote nt in inhibiting monocyte COX-2 activity than platelet TXB2 production. In contrast, aspirin (55 mu mol/L) largely suppressed platelet TXB2 production without affecting monocyte COX-2 activity. By using specific Western blot- techniques, we failed to detect COX-2 in platelets while COX-1 was readily detectable; Our results argue against the involvement of COX-2 in TX biosyn thesis-by activated platelets and consequently dispute platelet COX-2 expre ssion as an important mechanism of aspirin resistance.