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:
https://lup.lub.lu.se/record/3955908
- author
- Rahman, Milladur
LU
; Gustafsson, David
; Wang, Yongzhi
LU
; Thorlacius, Henrik
LU
and Braun, Oscar
LU
- organization
- publishing date
- 2014
- 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
- pmid:23855479
- 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
- 2016-04-01 11:12:28
- date last changed
- 2022-04-28 08:06:38
@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}},
doi = {{10.3109/09537104.2013.809520}},
volume = {{25}},
year = {{2014}},
}