Thromb Haemost 2000; 83(05): 777-784
DOI: 10.1055/s-0037-1613907
Review Article
Schattauer GmbH

Mechanisms Involved in the Antiplatelet Activity of Staphylococcus aureus Lipoteichoic Acid in Human Platelets

Joen-Rong Sheu
1  From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan
,
Cheng-Rong Lee
1  From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan
,
Chien-Huang Lin
1  From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan
,
George Hsiao
1  From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan
,
Wun-Chang Ko
1  From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan
,
Yao-Chang Chen
2  Department of Biomedical Engineering, Taipei, Taiwan
,
Mao-Hsiung Yen
3  Department of Pharmacology National Defense Medical Center, Taipei, Taiwan
› Author Affiliations
This work was supported by a grant from the National Science Council of Taiwan (NSC 89-2320-B-038-002-M53).
Further Information

Publication History

Received 28 September 1999

Accepted after revision 26 January 2000

Publication Date:
08 December 2017 (online)

Summary

In this study, Gram-positive Staphylococcus aureus lipoteichoic acid (LTA) dose-dependently (0.1-1.0 µg/ml) and time-dependently (10-60 min) inhibited platelet aggregation in human platelets stimulated by agonists. LTA also dose-dependently inhibited phosphoinositide breakdown and intracellular Ca+2 mobilization in human platelets stimulated by collagen. LTA (0.5 and 1.0 µg/ml) also significantly inhibited thromboxane A2 formation stimulated by collagen in human platelets. Moreover, LTA (0.1-1.0 µg/ml) dose-dependently decreased the fluorescence of platelet membranes tagged with diphenylhexatrience. Rapid phosphorylation of a platelet protein of Mr. 47,000 (P47), a marker of protein kinase C activation, was triggered by PDBu (30 nM). This phosphorylation was markedly inhibited by LTA (0.5 and 1.0 µg/ml) within a 10-min incubation period.

These results indicate that the antiplatelet activity of LTA may be involved in the following pathways: LTA’s effects may initially be due to induction of conformational changes in the platelet membrane, leading to a change in the activity of phospholipase C, and subsequent inhibition of phosphoinositide breakdown and thromboxane A2 formation, thereby leading to inhibition of both intracellular Ca+2 mobilization and phosphorylation of P47 protein. Therefore, LTA-mediated alteration of platelet function may contribute to bleeding diathesis in Gram-positive septicemic and endotoxemic patients.