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Mast cells protect against Pseudomonas aeruginosa-induced lung injury.

Junkins RD1, Carrigan SO2, Wu Z1, Stadnyk AW1, Cowley E3, Issekutz T1, Berman J4, Lin TJ5.

Am J Pathol. 2014 ;184(8):2310-21.

1Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada. and

2Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada. and

3Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada. and

4Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.and

5Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: [email protected]

 

Abstract

Pseudomonas aeruginosa, an opportunistic pathogen, is the leading cause of morbidity and mortality in immune-compromised individuals. Maintaining the integrity of the respiratory epithelium is critical for an effective host response to P. aeruginosa. Given the close spatial relationship between mast cells and the respiratory epithelium, and the importance of tightly regulated epithelial permeability during lung infections, we examined whether mast cells influence airway epithelial integrity during P. aeruginosa lung infection in a mouse model. We found that mast cell-deficient Kit(W-sh)/Kit(W-sh) mice displayed greatly increased epithelial permeability, bacterial dissemination, and neutrophil accumulation compared with wild-type animals after P. aeruginosa infection; these defects were corrected on reconstitution with mast cells. An in vitro Transwell co-culture model further demonstrated that a secreted mast cell factor decreased epithelial cell apoptosis and tumor necrosis factor production after P. aeruginosa infection. Together, our data demonstrate a previously unrecognized role for mast cells in the maintenance of epithelial integrity during P. aeruginosa infection, through a mechanism that likely involves prevention of epithelial apoptosis and tumor necrosis factor production. Our understanding of mechanisms of the host response to P. aeruginosa will open new avenues for the development of successful preventative and treatment strategies.

Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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Mast cells protect against Pseudomonas aeruginosa-induced lung injury.. Global Medical Discovery