title: The antiplatelet activity of Escherichia coli lipopolysaccharide is mediated through a nitric oxide/cyclic GMP pathway.
abstract: In this study, Escherichia coli LPS dose-dependently (100-500 microg/ml) and time-dependently (10-60 min) inhibited platelet aggregation in human and rabbit platelets stimulated by agonists. LPS also dose-dependently inhibited the intracellular Ca2+ mobilization in human platelets stimulated by collagen. In addition, LPS (200 and 500 microg/ml) significantly increased the formation of cyclic GMP but not cyclic AMP in platelets. LPS (200 microg/ml) significantly increased the production of nitrate within a 10-min incubation period. Furthermore, LPS also dose-dependently inhibited platelet aggregation induced by PDBu (30 nmol/l), a protein kinase C activator. These results indicate that the antiplatelet activity of E. coli LPS may be involved in the activation of a nitric oxide/cyclic GMP pathway in platelets, resulting in inhibition of platelet aggregation. Therefore, LPS-mediated alteration of platelet function may contribute to bleeding diathesis in septicemic and endotoxemic patients.
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan. sheujr@tmc.edu.tw
authors.forename: J R
authors.initials: JR
authors.lastname: Sheu
authors.forename: W C
authors.initials: WC
authors.lastname: Hung
authors.forename: C H
authors.initials: CH
authors.lastname: Su
authors.forename: C H
authors.initials: CH
authors.lastname: Lin
authors.forename: L W
authors.initials: LW
authors.lastname: Lee
authors.forename: Y M
authors.initials: YM
authors.lastname: Lee
authors.forename: M H
authors.initials: MH
authors.lastname: Yen
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology*; D004926:Escherichia coli; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D006152:Cyclic GMP