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

Joen Rong Sheu, George Hsiao, Cheng Rong Lee, Wen Chiung Chang, Ling Wen Lee, Ching Hua Su, Chien-Huang Lin

Research output: Contribution to journalArticlepeer-review

16 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 (i.e., thrombin and collagen). LTA also dose dependently inhibited intracellular Ca2+ mobilization in human platelets stimulated by collagen. In addition, LTA (0.5 and 1.0 μg/mL) dose dependently increased the formation of cyclic AMP but not cyclic GMP in platelets. LTA (0.5 and 1.0 μg/mL) did not significantly increase the production of nitrate within a 10-min incubation period. Rapid phosphorylation of a platelet protein of M(r) 47,000, a marker of protein kinase C activation, was triggered by PDBu (0.03 μM). This phosphorylation was dose dependently inhibited by LTA (0.5 and 1.0 μg/mL) within a 10-min incubation period. Furthermore, LTA (0.5 and 1.0 μg/mL) also inhibited platelet aggregation induced by PDBu (0.03 μM) in human platelets.These results indicate that the antiplatelet activity of LTA may be involved in the increase of cyclic AMP, leading to inhibition of intracellular Ca2+ mobilization and protein kinase C activity. Therefore, LTA-mediated alteration of platelet function may contribute to bleeding diathesis in septicemic and endotoxemic patients. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)249-258
Number of pages10
JournalThrombosis Research
Volume99
Issue number3
DOIs
Publication statusPublished - Jun 1 2000

Keywords

  • Cyclic AMP
  • Gram-positive bacteria
  • LTA
  • Platelet aggregation
  • Protein kinase C

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology

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