Evidence that Pseudomonas aeruginosa elastase does not inactivate the bronchial inhibitor in the presence of leukocyte elastase. Studies with cystic fibrosis sputum and with pure proteins.
Pseudomonas aeruginosa elastase has recently been shown to inactivate bronchial inhibitor, the major leukoproteinase inhibitor of the bronchial tree. To test if this in vitro finding is relevant to pathology, we have measured the leukocyte elastase inhibitory capacity and the immunoreactive levels of bronchial inhibitor in the acidified and neutralized sputum specimens from 15 patients with cystic fibrosis, 11 of whom were infected by P. aeruginosa and 10 of whom exhibited free bacterial elastase activity. The percentage of functionally active bronchial inhibitor in these acid-treated sputum specimens (i.e., concentration of active inhibitor/concentration of immunoreactive inhibitor X 100) was found to be 125 +/- 17%. It was positively correlated with the free leukocyte elastase concentration (r = 0.77, p less than 0.001) but not with the free bacterial elastase concentration (r = 0.46, p greater than 0.05). Therefore, in an in vivo situation, P. aeruginosa elastase does not necessarily inactivate the bronchial inhibitor. Experiments using pure proteins show that the inactivation process does not take place when leukocyte and P. aeruginosa elastase are added simultaneously to the inhibitor. This suggests that the bronchial inhibitor reacts preferentially with leukocyte elastase and that in its complexed form it is shielded from the inactivating action of P. aeruginosa elastase. In addition, the inhibitor recovered from the acid-induced dissociation of the leukocyte elastase-inhibitor complexes, exhibits a substantially higher specific activity than does the native molecule. This explains why the average functional activity of the bronchial inhibitor is significantly higher than 100% in sputum samples from patients with cystic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
J M
JM
Tournier
J
J
Jacquot
E
E
Puchelle
J G
JG
Bieth
D000293:Adolescent; D000328:Adult; D001980:Bronchi / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D010196:Pancreatic Elastase / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D013183:Sputum / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D000511:alpha-Macroglobulins / Q000378:metabolism
D011506:Proteins; D000511:alpha-Macroglobulins; D010196:Pancreatic Elastase