Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes.
The present study demonstrates that a granule fraction derived from human polymorphonuclear leukocytes possesses elastinolytic activity, and that the latter can be separated from the collagenase present in these cells. Properties of the human leukocyte elastase differ sufficiently from those of pancreatic elastases of different species as to suggest that the former enzyme is a distinct and separate entity. Thus, soybean trypsin inhibitor and salivary kallikrein inhibitor (Trasylol) fail to inhibit elastolysis by the pancreatic enzyme, but do inhibit the leukocyte elastinolytic agent. Elastolysis by human leukocyte granule extract does not show significant salt inhibition, whereas that catalyzed by pancreatic elastase is markedly reduced when ionic strength is increased to physiological levels. The leukocyte granule extract is at least 10 times more resistant to serum elastase inhibitor than is the purified pancreatic enzyme. Both enzymes show optimal elastolysis above pH 8.5, but the leukocyte factor still retains 50% of its maximal elastolytic activity at pH 6-7; whereas the activity of the pancreatic enzyme falls to 10% or less of its maximal value under the same conditions. The foregoing characteristics of the human leukocyte elastase suggest that it, rather than pancreatic (serum) elastase, may mediate pathological elastolysis during acute arteritis in man. In keeping with this suggestion, the present experiments also show that elastica staining of human arterial vessels is reduced by incubation of tissues with human leukocyte granule extracts in vitro.
D000328:Adult; D007611:Aprotinin / Q000494:pharmacology; D001769:Blood; D003094:Collagen; D004547:Elastic Tissue / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007249:Inflammation / Q000201:enzymology*; D007962:Leukocytes / Q000032:analysis / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000494:pharmacology; D011506:Proteins / Q000032:analysis; D012965:Sodium Chloride / Q000494:pharmacology; D014020:Tissue Extracts
D006454:Hemoglobins; D011506:Proteins; D014020:Tissue Extracts; D012965:Sodium Chloride; D003094:Collagen; D007611:Aprotinin; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase