title: Platelets support pulmonary recruitment of neutrophils in abdominal sepsis.
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.
  
  
  METHODS
  Prospective experimental study.
  
  
  METHODS
  University Hospital Research Unit.
  
  
  METHODS
  Male C57BL/6 mice.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Asaduzzaman
authors.forename: Shahram
authors.initials: S
authors.lastname: Lavasani
authors.forename: Milladur
authors.initials: M
authors.lastname: Rahman
authors.forename: Su
authors.initials: S
authors.lastname: Zhang
authors.forename: Oscar O
authors.initials: OO
authors.lastname: Braun
authors.forename: Bengt
authors.initials: B
authors.lastname: Jeppsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Thorlacius
mesh_terms: D000005:Abdomen; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D011654:Pulmonary Edema / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*