Neutral protease secretion by human monocytes. Effect of surface-bound immune complexes.
The effect of surface-bound immune complexes on the secretion of neutral proteases by human peripheral monocytes was examined. Monocytes cultured on 125I-fibrin secreted plasminogen activator in a continuous fashion. Monocytes incubated on 125I-fibrin with surface-bound immune complexes displayed a burst of plasminogen-independent fibrinolytic activity, whereas no release of plasminogen activator was observed through 21 h. The plasminogen-independent fibrinolytic enzymes were derived from monocytes and not from lymphocytes or contaminating polymorphonuclear neutrophils. The effects of various protease inhibitors on the secretion of plasminogen-dependent and independent enzymes were determined. Chymostatin selectively inhibited the monocyte-derived plasminogen activators. Similar effects of chymostatin were observed on human urokinase in the absence of cells. The predominant protease producing plasminogen-independent fibrinolysis exhibited responses to inhibitors characteristic of leukocyte elastase. When monocytes were cultured on 125I-fibrin with adherent immune complexes approximately equal to 40% of the solubilized radioactivity represented deiodination and not proteolysis. It was concluded that culture of human monocytes on surface-bound immune complexes stimulates the secretion of plasminogen-independent fibrinolytic proteases, primarily elastase, and of deiodinating enzymes. Under these conditions, plasminogen activator secretion is inhibited. Neutral proteases secreted from newly recruited monocytes may contribute to tissue injury in human diseases characterized by the presence of adherent immune complexes.
D000936:Antigen-Antibody Complex; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007455:Iodine / Q000378:metabolism; D008214:Lymphocytes / Q000201:enzymology; D009000:Monocytes / Q000166:cytology / Q000201:enzymology*; D009504:Neutrophils / Q000201:enzymology; D010447:Peptide Hydrolases / Q000097:blood*; D010958:Plasminogen / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D011480:Protease Inhibitors; D010958:Plasminogen; D007455:Iodine; D010447:Peptide Hydrolases