Mechanisms involved in the antiplatelet activity of Staphylococcus aureus lipoteichoic acid in human platelets

this study, Gram-positive Staphylococcus aureus lipoteichoic acid (LTA) dos e-dependently (0.1-1.0 mu g/ml) and time-dependently (10-60 min) inhibited platelet aggregation in human platelets stimulated by agonists. LTA also do se-dependently inhibited phosphoinositide breakdown and intracellular Ca+2 mobilization in human platelets stimulated by collagen. LTA (0.5 and 1.0 mu g/ml) also significantly inhibited thromboxane A, formation stimulated by collagen in human platelets. Moreover, LTA (0.1-1.0 mu g/ml) dose-dependent ly decreased the fluorescence of platelet membranes tagged with diphenylhex atrience. Rapid phosphorylation of a platelet protein of Mr. 47,000 (P47), a marker of protein kinase C activation, was triggered by PDBu (30 nM). Thi s phosphorylation was markedly inhibited by LTA (0.5 and 1.0 mu g/ml) withi n a 10-min incubation period. These results indicate that the antiplatelet activity of LTA may be involve d in the following pathways: LTA's effects may initially be due to inductio n of conformational changes in the platelet membrane, leading to a change i n the activity of phospholipase C, and subsequent inhibition of phosphoinos itide breakdown and thromboxane A(2) formation thereby leading to inhibitio n of both intracellular Ca+2 mobilization and phosphorylation of P47 protei n. Therefore, LTA-mediated alteration of platelet function may contribute t o bleeding diathesis in Gram-positive septicemic and endotoxemic patients.