Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody:KC complexes in a model of acute lung injury

Respiratory Research

Gustavo Matute-Bello²  Jon M Florence⁴  Agnieszka Krupa⁴  Anna Kurdowska⁴  Sean E Gill¹  William A Altemeier³  Alex W Farnand³  Sucheol Gil³ 

[1] The Centre for Critical Illness Research, Lawson Health Research Institute, Department of Medicine, Western University, London, ON, Canada;The Medical Research Service, Seattle VA Puget Sound Healthcare System, Seattle, WA, USA;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;The Department of Cellular and Molecular Biology, University of Texas Health Science Center, Tyler, TX, USA

关键词: Lipopolysaccharide;    Apoptosis;    Mechanical ventilation;    Cytokines;    Fas;    Inflammation;   

Others  :  796633
DOI  :  10.1186/1465-9921-13-91

 received in 2012-05-03, accepted in 2012-10-01,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Gil et al.; licensee BioMed Central Ltd.

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