Characteristics of fibrinolytic enzyme release from human monocytes.
We have investigated further two patterns of neutral protease secretion previously described in cultured human monocytes. Freshly isolated or cultured monocytes were plated onto 125I-fibrin either with or without adherent immune complexes. Fibrinolysis was quantified in the presence or absence of added plasminogen. Freshly isolated monocytes cultured on plain fibrin produced fibrinolysis primarily through secretion of plasminogen activator (PA), while contact with adherent complexes induced the release of plasminogen-independent fibrinolytic enzymes. In vitro differentiation of monocytes led to altered enzyme release. PA secretion rose six-fold over the first 3 days of culture, then decreased. Plasminogen-independent enzyme release fell 70% after 24 hr of culture then declined no further. Whereas adherent complexes inhibited secretion of PA in freshly isolated cells, such complexes stimulated PA activity after 3 or more days of culture. PA secretion from freshly isolated monocytes was inhibited by cycloheximide, indicating a requirement for protein synthesis, and by cytochalasin B. PA secretion was also reduced by the local anaesthetics ethanol, octanol, or lidocaine, but was enhanced by propranolol. The reduced PA activity of freshly isolated monocytes cultured on adherent immune complexes was partially reversed by ethanol or propranolol, but not by cytochalasin B. The plasminogen-independent fibrinolytic activity or monocytes on adherent complexes was enhanced by cytochalasin B, but unaffected by cychloheximide suggesting that the enzymes were granule-associated. This secretion was reduced by preincubation with 8-Br-cAMP and methyl isobutyl xanthine and by the local anaesthetics examined.
D000779:Anesthetics, Local / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology; D010447:Peptide Hydrolases / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism
D000779:Anesthetics, Local; D000936:Antigen-Antibody Complex; D005337:Fibrin; D010447:Peptide Hydrolases; D010960:Plasminogen Activators