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

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)777-784
Number of pages8
JournalThrombosis and Haemostasis
Volume83
Issue number5
Publication statusPublished - 2000

Keywords

  • Gram-positive bacteria
  • Lipoteichoic acid
  • Membrane fluidity
  • Platelet aggregation
  • Protein kinase C

ASJC Scopus subject areas

  • Hematology

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