CHARACTERISTICS OF FIBRINOLYTIC ENZYME-RELEASE FROM HUMAN-MONOCYTES

  • 1 January 1981
    • journal article
    • research article
    • Vol. 46  (1) , 214-224
Abstract
Two patterns of neutral protease secretion previously described in cultured human monocytes were further investigated. Freshly isolated or cultured monocytes were plated onto 125I-fibrin substrates 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); 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 6-fold over the first 3 days of culture, then decreased. Plasminogen-independent enzyme release fell 70% after 24 h of culture then declined no further. Whereas adherent complexes inhibited secretion of PA in freshly isolated cells, such complexes stimulated PA activity after 3 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 of monocytes on adherent complexes was enhanced by cytochalasin B, but unaffected by cycloheximide, suggesting that the enzymes were granule-associated. This secretion was reduced by preincubation with 8-bromo-cAMP methyl isobutyl xanthine and by the local anesthetics examined.