Antiplatelet activity of Staphylococcus aureus lipoteichoic acid is mediated through a cyclic AMP pathway

In this study, Gram-positive Staphylococcus aureus lipoteichoic acid (LTA) dose dependently (0.1-1.0 mu g/mL) and time dependently (10-60 min) inhibit ed platelet aggregation in human platelets stimulated by agonists (i.e., th rombin and collagen). LTA also dose dependently inhibited intracellular Ca2 + mobilization in human platelets stimulated by collagen. In addition, LTA (0.5 and 1.0 mu g/mL) dose dependently increased the formation of cyclic AM P but not cyclic CMP in platelets. LTA (0.5 and 1.0 mu g/mL) did not signif icantly increase the production of nitrate within a 10-min incubation perio d. Rapid phosphorylation of a platelet protein of M-r 47,000, a marker of p rotein kinase C activation, was triggered by PDBu (0.03 mu M). This phospho rylation was dose dependently inhibited by LTA (0.5 and 1.0 mu g/mL) within a 10-min incubation period. Furthermore, LTA (0.5 and 1.0 mu g/mL) also in hibited platelet aggregation induced by PDBu (0.03 mu M) in human platelets . These results indicate that the antiplatelet activity of LTA may be involve d in the increase of cyclic AMP, leading to inhibition of intracellular Ca2 + mobilization and protein kinase C activity. Therefore, LTA-mediated alter ation of platelet function may contribute to bleeding diathesis in septicem ic and endotoxemic patients. (C) 2000 Elsevier Science Ltd. All rights rese rved.