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Ticagrelor reduces neutrophil recruitment and lung damage in abdominal sepsis.

Rahman, Milladur LU ; Gustafsson, David; Wang, Yongzhi LU ; Thorlacius, Henrik LU and Braun, Oscar LU (2014) In Platelets 25(4). p.257-263
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Platelets
volume
25
issue
4
pages
257 - 263
publisher
Taylor & Francis
external identifiers
  • pmid:23855479
  • wos:000336950800006
  • scopus:84899943554
ISSN
1369-1635
DOI
10.3109/09537104.2013.809520
language
English
LU publication?
yes
id
0afd7dce-26f0-4bed-9cc8-3dc8bbacb4a7 (old id 3955908)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23855479?dopt=Abstract
date added to LUP
2013-08-02 12:21:01
date last changed
2017-09-17 04:20:50
@article{0afd7dce-26f0-4bed-9cc8-3dc8bbacb4a7,
  abstract     = {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.},
  author       = {Rahman, Milladur and Gustafsson, David and Wang, Yongzhi and Thorlacius, Henrik and Braun, Oscar},
  issn         = {1369-1635},
  language     = {eng},
  number       = {4},
  pages        = {257--263},
  publisher    = {Taylor & Francis},
  series       = {Platelets},
  title        = {Ticagrelor reduces neutrophil recruitment and lung damage in abdominal sepsis.},
  url          = {http://dx.doi.org/10.3109/09537104.2013.809520},
  volume       = {25},
  year         = {2014},
}