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Oscar Braun

Physician

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Ticagrelor reduces neutrophil recruitment and lung damage in abdominal sepsis.

Author

  • Milladur Rahman
  • David Gustafsson
  • Yongzhi Wang
  • Henrik Thorlacius
  • Oscar Braun

Summary, in English

Abstract Platelets play an important role in abdominal sepsis and P2Y12 receptor antagonists have been reported to exert anti-inflammatory effects. Herein, we assessed the impact of platelet inhibition with the P2Y12 receptor antagonist ticagrelor on pulmonary neutrophil recruitment and tissue damage in a model of abdominal sepsis. Wild-type C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Animals were treated with ticagrelor (100 mg/kg) or vehicle prior to CLP induction. Edema formation and bronchoalveolar neutrophils as well as lung damage were quantified. Flow cytometry was used to determine expression of platelet-neutrophil aggregates, neutrophil activation and CD40L expression on platelets. CLP-induced pulmonary infiltration of neutrophils at 24 hours was reduced by 50% in ticagrelor-treated animals. Moreover, ticagrelor abolished CLP-provoked lung edema and decreased lung damage score by 41%. Notably, ticagrelor completely inhibited formation of platelet-neutrophil aggregates and markedly reduced thrombocytopenia in CLP animals. In addition, ticagrelor reduced platelet shedding of CD40L in septic mice. Our data indicate that ticagrelor can reduce CLP-induced pulmonary neutrophil recruitment and lung damage suggesting a potential role for platelet antagonists, such as ticagrelor, in the management of patients with abdominal sepsis.

Department/s

  • Surgery
  • Cardiology

Publishing year

2014

Language

English

Pages

257-263

Publication/Series

Platelets

Volume

25

Issue

4

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Hematology

Status

Published

Research group

  • Surgery

ISBN/ISSN/Other

  • ISSN: 1369-1635