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Platelets support pulmonary recruitment of neutrophils in abdominal sepsis

Muhammad, Asad LU ; Lavasani, Shahram LU ; Rahman, Milladur LU ; Zhang, Su LU ; Braun, Oscar LU ; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2009) In Critical Care Medicine 37(4). p.1389-1396
Abstract
Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung. Design: Prospective experimental study. Setting. University Hospital Research Unit. Subject. Male C57BL/6 mice. Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and... (More)
Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung. Design: Prospective experimental study. Setting. University Hospital Research Unit. Subject. Male C57BL/6 mice. Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction. Measurements and Main Results. CLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1. Conclusions: These data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis. (Crit Care Med 2009; 37:1389-1396) (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
lung, platelets, adhesion, neutrophils, sepsis
in
Critical Care Medicine
volume
37
issue
4
pages
1389 - 1396
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000264699000030
  • pmid:19242347
  • scopus:67650472342
ISSN
1530-0293
DOI
10.1097/CCM.0b013e31819ceb71
language
English
LU publication?
yes
id
dced5300-a02c-4970-9a15-ee20b088b827 (old id 1401114)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19242347?dopt=Abstract
date added to LUP
2009-06-15 11:29:40
date last changed
2017-12-17 03:27:56
@article{dced5300-a02c-4970-9a15-ee20b088b827,
  abstract     = {Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung. Design: Prospective experimental study. Setting. University Hospital Research Unit. Subject. Male C57BL/6 mice. Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction. Measurements and Main Results. CLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1. Conclusions: These data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis. (Crit Care Med 2009; 37:1389-1396)},
  author       = {Muhammad, Asad and Lavasani, Shahram and Rahman, Milladur and Zhang, Su and Braun, Oscar and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {1530-0293},
  keyword      = {lung,platelets,adhesion,neutrophils,sepsis},
  language     = {eng},
  number       = {4},
  pages        = {1389--1396},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Critical Care Medicine},
  title        = {Platelets support pulmonary recruitment of neutrophils in abdominal sepsis},
  url          = {http://dx.doi.org/10.1097/CCM.0b013e31819ceb71},
  volume       = {37},
  year         = {2009},
}