Cathepsin-G interferes with clearance of Pseudomonas aeruginosa from mouse lungs.
The cystic fibrosis airway is susceptible to Pseudomonas aeruginosa infection, which stimulates an intense inflammatory response leading to airway obstruction and bronchiectasis. Neutrophils migrate into the airway, and once there, release high concentrations of neutral serine proteases during phagocytosis and in death. In particular, neutrophil elastase is central to progression of bronchiectasis by interfering with bacterial clearance and directly perpetuating the inflammatory response in the airway. Using a murine model of endobronchial inflammation, we found that a different neutrophil-derived serine protease, cathepsin G, inhibited the host's ability to clear Pseudomonas from the lung, based on a 1-log reduction in bacteria recovered from cathepsin G-deficient mice. Higher antibody concentrations were found in respiratory epithelial lining fluid from mice lacking cathepsin G, but there was no difference in other opsonins, such as surfactant proteins A and D. Chemokine levels measured in the lung correlated with bacterial burden and not the animal's genotype, indicating that airway inflammation was not affected by the presence (or absence) of specific serine proteases. These findings suggest that cathepsin G interferes with airway defenses, showing that proteases other than neutrophil elastase have roles in the pathogenesis of suppurative airway diseases.
Sedor
Julia
J
Mallinkrodt Department of Pediatrics, WA University School of Medicine, St. Louis, MO 63110, USA.
Hogue
Lisa
L
Akers
Kathryn
K
Boslaugh
Sarah
S
Schreiber
John
J
Ferkol
Thomas
T
D000818:Animals; D001991:Bronchitis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D056649:Cathepsin G; D002403:Cathepsins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003550:Cystic Fibrosis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D019272:Leukocyte Elastase / Q000172:deficiency / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000201:enzymology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; C534096:Ctsg protein, mouse; D019272:Leukocyte Elastase