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Updated: Nov 14, 2025
Pseudomonas aeruginosa Induced Lung Injury Model
Published on: October 29, 2014
LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic
Lisa C Hennemann1,2, Shantelle L LaFayette1,2, Julien K Malet2
1Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Abstract:
Pseudomonas aeruginosa causes chronic airway infections, a major determinant of lung inflammation and damage in cystic fibrosis (CF). Loss-of-function lasR mutants commonly arise during chronic CF infections, are associated with accelerated lung function decline in CF patients and induce exaggerated neutrophilic inflammation in model systems. In this study, we investigated how lasR mutants modulate airway epithelial membrane bound ICAM-1 (mICAM-1), a surface adhesion molecule, and determined its impact on neutrophilic inflammation in vitro and in vivo. We demonstrated that LasR-deficient strains induce increased mICAM-1 levels in airway epithelial cells compared to wild-type strains, an effect attributable to the loss of mICAM-1 degradation by LasR-regulated proteases and associated with enhanced neutrophil adhesion. In a subacute airway infection model, we also observed that lasR mutant-infected mice displayed greater airway epithelial ICAM-1 expression and increased neutrophilic pulmonary inflammation. Our findings provide new insights into the intricate interplay between lasR mutants, LasR-regulated proteases and airway epithelial ICAM-1 expression, and reveal a new mechanism involved in the exaggerated inflammatory response induced by lasR mutants.
Insights
Pseudomonas aeruginosa lasR mutants, common in cystic fibrosis (CF) lung infections, increase airway epithelial ICAM-1. This heightened expression drives enhanced neutrophil adhesion and inflammation, worsening lung damage in CF patients.
Area of Science:
- Microbiology
- Immunology
- Pulmonary Medicine
Background:
- Pseudomonas aeruginosa chronic airway infections are detrimental in cystic fibrosis (CF).
- Loss-of-function lasR mutants are linked to faster lung function decline and heightened inflammation in CF.
- Membrane-bound ICAM-1 (mICAM-1) is a key adhesion molecule in airway inflammation.
Purpose of the Study:
- To investigate how lasR mutants affect airway epithelial mICAM-1 expression.
- To determine the impact of altered mICAM-1 on neutrophilic inflammation in vitro and in vivo.
Main Methods:
- Comparing mICAM-1 levels in airway epithelial cells infected with lasR mutants versus wild-type P. aeruginosa.
- Assessing neutrophil adhesion to epithelial cells.
- Analyzing ICAM-1 expression and neutrophilic inflammation in a mouse airway infection model.
Main Results:
- LasR-deficient P. aeruginosa strains significantly increased mICAM-1 levels in airway epithelial cells.
- Increased mICAM-1 resulted from reduced degradation by LasR-regulated proteases, leading to enhanced neutrophil adhesion.
- In vivo, lasR mutant infection correlated with higher airway epithelial ICAM-1 and increased pulmonary neutrophilic inflammation.
Conclusions:
- LasR mutants disrupt mICAM-1 regulation, contributing to exaggerated neutrophilic inflammation in CF airways.
- Loss of LasR function leads to increased mICAM-1, promoting neutrophil adhesion and lung damage.
- This study elucidates a novel mechanism linking lasR mutants, proteases, and ICAM-1 in P. aeruginosa-induced lung inflammation.
