The antiplatelet activity of Escherichia coli lipopolysaccharide is mediated through a nitric oxide/cyclic GMP pathway
Corresponding Author
Dr J. R. Sheu
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Joen-Rong Sheu, Graduate Institute of Medical Sciences, Taipei Medical College, No 250, Wu-Shing Street, Taipei 110, Taiwan Tel/Fax: +886–2–27390450 E-mail: [email protected]Search for more papers by this authorW. C. Hung
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Search for more papers by this authorC. H. Su
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Search for more papers by this authorC. H. Lin
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Search for more papers by this authorL. W. Lee
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Search for more papers by this authorY. M. Lee
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan
Search for more papers by this authorM. H. Yen
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Dr J. R. Sheu
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Joen-Rong Sheu, Graduate Institute of Medical Sciences, Taipei Medical College, No 250, Wu-Shing Street, Taipei 110, Taiwan Tel/Fax: +886–2–27390450 E-mail: [email protected]Search for more papers by this authorW. C. Hung
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Search for more papers by this authorC. H. Su
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Search for more papers by this authorC. H. Lin
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Search for more papers by this authorL. W. Lee
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan
Search for more papers by this authorY. M. Lee
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan
Search for more papers by this authorM. H. Yen
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan
Search for more papers by this authorAbstract
Abstract: In this study, Escherichia coli LPS dose-dependently (100–500 μg/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 μg/ml) significantly increased the formation of cyclic GMP but not cyclic AMP in platelets. LPS (200 μg/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.
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