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Platelets support pulmonary recruitment of neutrophils in abdominal sepsis

Author:
  • Asad Muhammad
  • Shahram Lavasani
  • Milladur Rahman
  • Su Zhang
  • Oscar Braun
  • Bengt Jeppsson
  • Henrik Thorlacius
Publishing year: 2009
Language: English
Pages: 1389-1396
Publication/Series: Critical Care Medicine
Volume: 37
Issue: 4
Document type: Journal article
Publisher: Lippincott Williams & Wilkins

Abstract english

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)

Keywords

  • Cardiac and Cardiovascular Systems
  • Surgery
  • lung
  • platelets
  • adhesion
  • neutrophils
  • sepsis

Other

Published
  • Surgery Research
  • ISSN: 1530-0293
E-mail: oscar.braun [at] med.lu.se

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