Elastase secretion by stimulated macrophages. Characterization and regulation.
Thioglycolate-stimulated mouse peritoneal macrophages secrete a Proteinase which degrades insoluble elastin. There is little elastase activity in cell lysates but the bulk of the enzyme accumulates extracellularly during culture in serum-free medium. The secretion of elastase is sustained for over 12 days in culture and continued secretion of elastase requires protein synthesis. Unstimulated macrophages secrete very little elastase activity but can be triggered to secrete higher levels of this enzyme by phagocytosis and intracellular storage of latex particles. The macrophages elastase is a distinctive proteinase differing from the elastases of pancreas and granulocytes and is distinct from the other secreted proteinases of macrophages, namely, collagenase and plasminogen activator. The macrophages elastase is a serine proteinase and is inhibited by di-isopropyl phosphoro-fluoridate, ovoinhibitor, EDTA, dithiothretiol, and serum. Its activity is little affected by soybean trypsin inhibitor, turkey ovomucoid and chloromethyl ketones derived from tosyl lysine, tosyl phenylalanine, and acetyltetra alanine. Hydrolysis by macrophage elastase of chromogenic ester substrates for pancreatic elastase could not be detected. Elastase secretion by stimulated macrophages exceeds that by primary and established fibroblast cell strains. It is likely that elastase secretion by macrophages plays a major role in the pathogenesis of chronic destructive pulmonary diseases such as emphysema.
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D002478:Cells, Cultured; D004796:Clinical Enzyme Tests; D004549:Elastin; D004950:Esterases / Q000032:analysis; D005260:Female; D005779:Immunodiffusion; D007840:Latex; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D003012:Microbial Collagenase / Q000032:analysis; D008863:Microspheres; D010196:Pancreatic Elastase / Q000032:analysis / Q000378:metabolism*; D010587:Phagocytosis; D012965:Sodium Chloride / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013864:Thioglycolates / Q000494:pharmacology
D007840:Latex; D013864:Thioglycolates; D012967:Sodium Dodecyl Sulfate; D012965:Sodium Chloride; D004549:Elastin; D004950:Esterases; D010196:Pancreatic Elastase; D003012:Microbial Collagenase