Activation and damage of cultured airway epithelial cells by human elastase and cathepsin G.
Accumulation of polymorphonuclear neutrophils (PMN) and epithelium damage have often been described during airway inflammation. We studied the effects of two PMN-derived proteinases, namely elastase and cathepsin G, on guinea-pig tracheal epithelial cells in culture. Both proteinases activated tracheal epithelial cells in terms of prostaglandin (PG) E2 production. A concentration- and time-dependent effect was observed with 10 micrograms/ml and 6 h as the optimal conditions for both enzymes. Optical microscopic studies confirmed an effect on tracheal epithelial cells as intercellular gaps were observed upon incubation of the monolayers with proteinases. A small cytotoxic effect was observed after 1 h incubation but remained stable up to 6 h. This cytotoxic effect, more pronounced with elastase than with cathepsin G, was dissociated from PGE2 formation.
Nahori
M A
MA
Unité Associée IP/INSERM no. 285, Institut Pasteur, Paris, France.
Renesto
P
P
Vargaftig
B B
BB
Chignard
M
M
D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D010196:Pancreatic Elastase / Q000633:toxicity*; D012697:Serine Endopeptidases; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D015232:Dinoprostone