The role of bacterial proteases in the pathogenesis of cystic fibrosis.
Among the roles of mediators damaging the respiratory epithelium in patients with cystic fibrosis (CF) during the course of chronic, purulent bronchitis, that of neutrophil proteases is well established. The role of bacterial proteases is less well known. Among all pathogens colonizing the airways in CF, Pseudomonas aeruginosa is quantitatively the dominant pathogen; Staphylococcus aureus and Haemophilus influenzae are present in lower numbers. Anaerobic bacteria may be detected in numbers exceeding those of Staphylococcus aureus and Haemophilus influenzae. Among all enzymes secreted by these bacterial strains, Pseudomonas elastase and alkaline protease were shown to be secreted in vivo over prolonged periods in the airways. These enzymes, mainly elastase, have proteolytic activity on many proteins involved in host defense mechanisms, often the same as those hydrolyzed by neutrophil proteases. Pseudomonas elastase has damaging effects on the respiratory epithelium; it has recently also been shown to augment the permeability of the respiratory epithelium cultured in vitro by proteolytic attack of tight junctions. The potential role of proteases and other enzymes secreted by anaerobic bacteria has not been studied in this disease. In conclusion, bacterial proteases secreted in vivo may play a role in the pathogenesis of the airway disease in CF; their relative importance to the role of host proteases is, however, often difficult to determine.
Department of Pediatrics, University Hospital of Geneva, Switzerland.
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D003550:Cystic Fibrosis / Q000201:enzymology* / Q000382:microbiology*; D010450:Endopeptidases / Q000502:physiology*; D006193:Haemophilus influenzae / Q000201:enzymology; D006801:Humans; D010196:Pancreatic Elastase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D013183:Sputum / Q000201:enzymology / Q000382:microbiology
D010450:Endopeptidases; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase