The antiplatelet activity of Escherichia coli lipopolysaccharide is mediated through a nitric oxide cyclic GMP pathway

In this study, Escherichia coli LPS dose-dependently (100-500 mu g/ mi) and time-dependently (10-60 min) inhibited platelet aggregation in human and r abbit platelets stimulated by agonists. LPS also dose-dependently inhibited the intracellular Ca2+ mobilization in human platelets stimulated by colla gen. In addition, LPS (200 and 500 mu g/ml) significantly increased the for mation of cyclic GMP but not cyclic AMP in platelets. LPS (200 mu g/ml) sig nificantly increased the production of nitrate within a 10-min incubation p eriod. Furthermore, LPS also dose-dependently inhibited platelet aggregatio n induced by PDBu (30 nmol/l), a protein kinase C activator. These results indicate that the antiplatelet activity of E. coli LPS may be involved in t he activation of a nitric oxide/cyclic GMP pathway in platelets, resulting in inhibition of platelet aggregation. Therefore, LPS-mediated alteration o f platelet function may contribute to bleeding diathesis in septicemic and endotoxemic patients.