title: P-selectin glycoprotein-ligand-1 regulates pulmonary recruitment of neutrophils in a platelet-independent manner in abdominal sepsis.
abstract: OBJECTIVE
  Neutrophil-mediated lung injury is an insidious feature in sepsis although the mechanisms regulating pulmonary recruitment of neutrophils remain elusive. Here, we investigated the role of P-selectin glycoprotein-ligand-1 (PSGL-1) in sepsis-induced neutrophil recruitment and tissue injury in the lung.
  
  
  METHODS
  Bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, oedema formation and CXC chemokines were determined 24 h after caecal ligation and puncture (CLP) in mice. Animals were pretreated with a control antibody, monoclonal antibodies directed against PSGL-1 and P-selectin as well as a platelet-depleting antibody directed against GP1balpha.
  
  
  RESULTS
  CLP caused pulmonary damage characterized by oedema formation, neutrophil infiltration and increased levels of CXC chemokines in the lung. Immunoneutralization of PSGL-1 or P-selectin reduced CLP-induced neutrophil recruitment in the bronchoalveolar space by more than 56% and lung myeloperoxidase activity by 62%. Notably, the inhibitory effect of the anti-PSGL-1 antibody on sepsis-induced neutrophil infiltration was also observed in platelet-depleted mice. Moreover, inhibition of PSGL-1 and P-selectin abolished CLP-induced oedema formation and tissue damage in the lung. CLP-induced formation of CXC chemokines was not changed in mice pretreated with the anti-PSGL-1 and anti-P-selectin antibodies.
  
  
  CONCLUSIONS
  These data demonstrate that PSGL-1 plays a key role in pulmonary infiltration of neutrophils as well as lung oedema associated with abdominal sepsis. Moreover, our findings suggest that PSGL-1-dependent neutrophil recruitment is independent of circulating platelets. Thus, these novel findings indicate that PSGL-1 may be a useful target to protect against sepsis-induced accumulation of neutrophils and tissue damage in the lung.
authors.affiliation: Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Asaduzzaman
authors.forename: Milladur
authors.initials: M
authors.lastname: Rahman
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 / Q000276:immunology; D019743:Chemokines, CXC / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000276:immunology; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D019743:Chemokines, CXC; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D009195:Peroxidase