Compromised inhibition of human lung lavage cell elastases.
Increased elastinolytic activity has been correlated with the degree of lung damage occurring in a variety of lung diseases including cystic fibrosis; serine proteinase inhibitors are currently on trial for the treatment of some lung disorders. However, human lung lavage cells also secrete metallo-dependent elastases. Here we show, for the first time, that whilst these are readily inhibited by EDTA, inhibition of serine elastases using serpins (serine proteinase inhibitors) is not always possible. This may reflect inactivation of serpins by uninhibited metalloproteinases and oxidants in a low protein milieu. Thus, the therapeutic inhibition of excessive elastinolytic activity may require a combination of inhibitors to work efficiently.
Smith
S F
SF
Department of Medicine, Charing Cross and Westminster Medical School, London, UK.
Roberts
N A
NA
Guz
A
A
Tetley
T D
TD
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017077:Culture Media, Conditioned; D004492:Edetic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D019272:Leukocyte Elastase; D008168:Lung / Q000166:cytology / Q000201:enzymology*; D008171:Lung Diseases / Q000188:drug therapy / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology; D016676:Macrophages, Alveolar / Q000201:enzymology; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D015843:Serpins / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D015843:Serpins; D000515:alpha 1-Antitrypsin; D004492:Edetic Acid; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase