title: Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody:KC complexes in a model of acute lung injury.
abstract: BACKGROUND
  Exposure to mechanical ventilation enhances lung injury in response to various stimuli, such as bacterial endotoxin (LPS). The Fas/FasL system is a receptor ligand system that has dual pro-apoptotic and pro-inflammatory functions and has been implicated in the pathogenesis of lung injury. In this study we test the hypothesis that a functioning Fas/FasL system is required for the development of lung injury in mechanically ventilated mice.
  
  
  METHODS
  C57BL/6 (B6) and Fas-deficient lpr mice were exposed to either intra-tracheal PBS followed by spontaneous breathing or intra-tracheal LPS followed by four hours mechanical ventilation with tidal volumes of 10 mL/kg, respiratory rate of 150 breaths per minute, inspired oxygen 0.21 and positive end expiratory pressure (PEEP) of 3 cm of water.
  
  
  RESULTS
  Compared with the B6 mice, the lpr mice showed attenuation of the neutrophilic response as measured by decreased numbers of BAL neutrophils and lung myeloperoxidase activity. Interestingly, the B6 and lpr mice had similar concentrations of pro-inflammatory cytokines, including CXCL1 (KC), and similar measurements of permeability and apoptosis. However, the B6 mice showed greater deposition of anti-KC:KC immune complexes in the lungs, as compared with the lpr mice.
  
  
  CONCLUSIONS
  We conclude that a functioning Fas/FasL system is required for full neutrophilic response to LPS in mechanically ventilated mice.
authors.affiliation: The Center for Lung Biology, Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Washington, 850 Republican Street, Box 351082, Seattle, WA 98109, USA.
authors.forename: Sucheol
authors.initials: S
authors.lastname: Gil
authors.forename: Alex W
authors.initials: AW
authors.lastname: Farnand
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
authors.forename: Sean E
authors.initials: SE
authors.lastname: Gill
authors.forename: Anna
authors.initials: A
authors.lastname: Kurdowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Krupa
authors.forename: Jon M
authors.initials: JM
authors.lastname: Florence
authors.forename: Gustavo
authors.initials: G
authors.lastname: Matute-Bello
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D054360:Chemokine CXCL1 / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018375:Neutrophil Activation / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology; D012121:Respiration, Artificial / Q000009:adverse effects*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C491899:Fas protein, mouse; D019014:fas Receptor