Stimulation of secretion into human and feline airways by Pseudomonas aeruginosa proteases.
We have investigated the effect of elastase and alkaline protease from Pseudomonas aeruginosa on airway secretion into the trachea of anesthetized cats and from human bronchial mucosa in vitro. Secretory macromolecules were radiolabeled biosynthetically with two precursors in the cat, [3H]glucose and [35S]sulfate, and with [35S]-sulfate only in human tissue. Both enzymes (2.6 x 10(-9) to 1.3 x 10(-6)M elastase and 8 x 10(-9) to 2.4 x 10(-6)M alkaline protease) released radiolabeled macromolecules in a concentration-dependent manner from the two preparations. Purified elastase, 1.3 x 10(-6)M, released radiolabeled macromolecules (delta 3H = +397 +/- 72%, delta 35S 225 +/- 40% over control, P less than 0.001) and periodic acid-Schiff- (PAS) reactive glycoconjugates (delta PAS = +4.1 +/- 0.96 micrograms/min or +102 +/- 20%; P less than 0.01) from cat trachea, as did alkaline protease, 2.4 x 10(-6)M (delta 3H = +356 +/- 57%, delta 35S = +176 +/- 25%, delta PAS = +7.5 +/- 1.3 micrograms/min or 194 +/- 36%, P less than 0.001). Increases in 3H exceeded those of 35S, suggesting surface epithelium as the main source of secretion. Inhibition of enzyme activity abolished secretory effects. Both enzymes also stimulated secretion from human bronchus (e.g., with elastase, 1.3 x 10(-6)M: delta 35S = +331 +/- 67%, delta PAS = +4.3 +/- 0.92 micrograms/min or +131 +/- 24%, P less than 0.001; with alkaline protease, 2.4 x 10(-6)M: delta 35S = +220 +/- 67%, delta PAS = +12.7 +/- 3.2 micrograms/min or +575 +/- 245%, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Somerville
M
M
Department of Physiology, St. George's Hospital Medical School, London, United Kingdom.
Richardson
P S
PS
Rutman
A
A
Wilson
R
R
Cole
P J
PJ
D000818:Animals; D001426:Bacterial Proteins; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002415:Cats; D010450:Endopeptidases / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000494:pharmacology; D008854:Microscopy, Electron; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D012697:Serine Endopeptidases / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D001426:Bacterial Proteins; D010450:Endopeptidases; C038495:Pseudomonas serine proteinase; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa