Elastase-induced changes in lung function: relationship to morphometry and effect of drugs.
Intratracheal administration of porcine pancreatic elastase (PPE) produced a dose related decline in lung function, as assessed by changes in dynamic lung compliance (C(dyn)) in New Zealand White rabbits. This occurred within 24 h of administration and persisted for 56 days (n=6). These lung function changes were accompanied by histological evidence of emphysema in the lungs and were not mimicked by intratracheal administration of the proteolytic enzyme trypsin. Neither the lung function nor the histological changes induced by elastase could be prevented or reversed by either the glucocorticosteroid, dexamethasone, or all trans retinoic acid (ATRA).Our data suggest that local administration of elastase to the lungs of rabbits may provide a convenient way to assess the effects of drugs on the changes induced by elastase in airways.
Nishi
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Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, Kings College London, 5th Floor, Hodgkin Building, Guy's Campus, London Bridge, London SE1 9RT, UK.
Boswell
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V
Ansari
T
T
Piprawala
F
F
Satchi
S
S
Page
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CP
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004646:Emphysema / Q000139:chemically induced / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use; D008297:Male; D010196:Pancreatic Elastase / Q000633:toxicity*; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011817:Rabbits; D013552:Swine; D017211:Treatment Failure; D014212:Tretinoin / Q000627:therapeutic use
D000970:Antineoplastic Agents; D005938:Glucocorticoids; D014212:Tretinoin; D003907:Dexamethasone; D010196:Pancreatic Elastase