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Inactivation of human bronchial mucosal proteinase inhibitor by Pseudomonas aeruginosa elastase
Abstract:
Human bronchial mucus contains an acid-stable proteinase inhibitor called bronchial mucous inhibitor (BMI) that apparently protects the upper airways from proteolysis by polymorphonuclear leukocyte (PMN) elastase and cathepsin G, and infections of Pseudomonas aeruginosa, which also produces an elastase, can result in considerable lung damage. The possible role of BMI in protecting the lung from proteolytic attack in the presence of P. aeruginosa elastase (a zinc metalloprotease) was investigated. The BMI not only failed to inhibit P. aeruginosa elastase but the ability of BMI to inhibit PMN elastase and cathepsin G was rapidly lost in the presence of the bacterial elastase. The P. aeruginosa elastase also freed active PMN elastase from complexes with BMI, resulting in elastin digestion by both enzymes. The proteolysis of lung tissue observed with P. aeruginosa infections may be caused by a combination of bacterial and PMN proteases. Elastase and cathepsin G released from leukocytes, attracted to P. aeruginosa infection sites, would be free to attack the bronchial tissues after BMI inactivation by P. aeruginosa elastase, adding to the damage caused by the bacterial protease(s).
Insights
Bronchial mucous inhibitor (BMI) does not inhibit Pseudomonas aeruginosa elastase. Instead, the bacterial elastase inactivates BMI, allowing neutrophil proteases to damage lung tissue during infection.
Area of Science:
- Pulmonary Medicine
- Microbiology
- Biochemistry
Background:
- Human bronchial mucus contains bronchial mucous inhibitor (BMI), an acid-stable proteinase inhibitor.
- BMI protects the upper airways from proteolysis by polymorphonuclear leukocyte (PMN) elastase and cathepsin G.
- Pseudomonas aeruginosa infections can cause significant lung damage due to bacterial elastase production.
Purpose of the Study:
- To investigate the role of BMI in protecting the lung from proteolytic attack by P. aeruginosa elastase.
- To determine if P. aeruginosa elastase affects BMI's inhibitory function against human proteases.
Main Methods:
- In vitro assays were performed to assess the interaction between P. aeruginosa elastase and BMI.
- The ability of BMI to inhibit PMN elastase and cathepsin G was measured in the presence of P. aeruginosa elastase.
- Elastin digestion assays were conducted to evaluate protease activity.
Main Results:
- BMI failed to inhibit P. aeruginosa elastase.
- P. aeruginosa elastase rapidly inactivated BMI's ability to inhibit PMN elastase and cathepsin G.
- P. aeruginosa elastase released active PMN elastase from BMI complexes, leading to elastin digestion by both enzymes.
Conclusions:
- BMI does not protect against P. aeruginosa elastase.
- P. aeruginosa elastase contributes to lung tissue proteolysis by inactivating BMI and releasing active PMN proteases.
- Lung damage during P. aeruginosa infections may result from a synergistic action of bacterial and host proteases.