Mechanisms involved in the antiplatelet activity of Escherichia coli lipopolysaccharide in human platelets

J. R. Sheu, W. C. Hung, Y. C. Kan, Y. M. Lee, M. H. Yen

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

In this study, Escherichia coli lipopolysaccharide (LPS) dose- dependently (100-300 μg/ml) and time-dependently (10-60 min) inhibited platelet aggregation in human platelets stimulated by agonists. LPS also dose-dependently inhibited the phosphoinositide breakdown and the intracellular Ca+2 mobilization in human platelets stimulated by collagen. LPS (300 μg/ml) also significantly inhibited the thromboxane A2 formation stimulated by collagen in human platelets. Moreover, LPS (100-300 μg/ml) dose-dependently decreased the fluorescence of platelet membranes tagged with diphenylhexatrience. In addition, LPS (200 and 300 μg/ml) significantly increased the formation of cyclic GMP but not cyclic AMP in platelets. LPS (200 μg/ml) also significantly increased the production of nitrate within a 30 min incubation period. Rapid phosphorylation of a platelet protein of M(r) 47 000, a marker of protein kinase C activation, was triggered by phorbol- 12-13-dibutyrate (PDBu, 50 nM). This phosphorylation was markedly inhibited by LPS (200 μg/ml) within a 30 min incubation period. These results indicate that the antiplatelet activity of LPS may be involved in two important pathways. (1) LPS may induce conformational changes in the platelet membrane, leading to change in the activity of phospholipase C, (2) LPS also activated the formation of nitric oxide (NO)/cyclic GMP in human platelets, resulting in inhibition of platelet aggregation. Therefore, LPS-mediated alteration of platelet function may contribute to bleeding diathesis in septicaemic and endotoxaemic patients.

Original languageEnglish
Pages (from-to)29-38
Number of pages10
JournalBritish Journal of Haematology
Volume103
Issue number1
DOIs
Publication statusPublished - 1998

Keywords

  • LPS
  • Membrane fluidity
  • Nitric oxide
  • Phosphoinositide breakdown
  • Protein kinase C.

ASJC Scopus subject areas

  • Hematology

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