Alpha-1 antitrypsin reduces severity of pseudomonas pneumonia in mice and inhibits epithelial barrier disruption and pseudomonas invasion of respiratory epithelial cells

Frontiers in Public Health
G B PottLeland Shapiro

Abstract

Nosocomial pneumonia (NP) is the third most common hospital-acquired infection and the leading cause of death due to hospital-acquired infection in the US. During pneumonia and non-pneumonia severe illness, respiratory tract secretions become enriched with the serine protease neutrophil elastase (NE). Several NE activities promote onset and severity of NP. NE in the airways causes proteolytic tissue damage, augments inflammation, may promote invasion of respiratory epithelium by bacteria, and disrupts respiratory epithelial barrier function. These NE activities culminate in enhanced bacterial replication, impaired gas exchange, fluid intrusion into the airways, and loss of bacterial containment that can result in bacteremia. Therefore, neutralizing NE activity may reduce the frequency and severity of NP. We evaluated human alpha-1 antitrypsin (AAT), the prototype endogenous NE inhibitor, as a suppressor of bacterial pneumonia and pneumonia-related pathogenesis. In AAT(+/+) transgenic mice that express human AAT in lungs, mortality due to Pseudomonas aeruginosa (P.aer) pneumonia was reduced 90% compared to non-transgenic control animals. Exogenous human AAT given to non-transgenic mice also significantly reduced P.aer pneumonia ...Continue Reading

Citations

Mar 25, 2015·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Lael M YonkerAlessandra Bragonzi
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May 10, 2020·Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology]·Silvia Guzman BeltránHaydee Torres Guerrero
Apr 3, 2020·International Journal of Environmental Research and Public Health·Alessandro SanduzziMarialuisa Bocchino
Nov 27, 2020·Medical Hypotheses·Xiyuan BaiEdward D Chan
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Methods Mentioned

BETA
bronchoalveolar lavage
transgenic

Software Mentioned

Prism
GraphPad

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