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

Joen-Rong Sheu; Cheng-Rong Lee; Chien-Huang Lin; George Hsiao; Wun-Chang Ko; Yao-Chang Chen; Mao-Hsiung Yen

doi:10.1055/s-0037-1613907

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

¹From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan

,

Cheng-Rong Lee

¹From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan

,

Chien-Huang Lin

¹From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan

,

George Hsiao

¹From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan

,

Wun-Chang Ko

¹From the Graduate Institute of Medical Sciences a n d Department of Pharmacology, Taipei Medical College, Taipei, Taiwan

,

Yao-Chang Chen

²Department of Biomedical Engineering, Taipei, Taiwan

,

Mao-Hsiung Yen

³Department of Pharmacology National Defense Medical Center, Taipei, Taiwan

› Institutsangaben

Abstract

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.

Key words

Gram-positive bacteria - lipoteichoic acid - platelet aggregation - membrane fluidity - protein kinase C

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