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P‐selectin glycoprotein‐ligand‐1 regulates pulmonary recruitment of neutrophils in a platelet‐independent manner in abdominal sepsis
Author(s) -
Asaduzzaman Muhammad,
Rahman Milladur,
Jeppsson Bengt,
Thorlacius Henrik
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2008.00021.x
Subject(s) - sepsis , myeloperoxidase , lung , infiltration (hvac) , immunology , platelet , chemokine , medicine , p selectin , selectin , bronchoalveolar lavage , neutrophil extracellular traps , inflammation , platelet activation , physics , thermodynamics
Background and purpose: 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. Experimental approach: 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 GP1bα. Key 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 and implications: 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.