INHIBITION OF PLASMINOGEN ACTIVATOR SECRETION BY CYCLIC-AMP IN A MACROPHAGE-LIKE CELL LINE

Abstract

The continuous cell line, J774.2, exhibits many macrophage-like functions such as latex and Fc-mediated phagocytosis, antibody [Ab]-mediated phagocytosis, Ab mediated cytotoxicity, chemotaxis and lysozyme secretion. Cyclic[c]AMP stimulates Fc-mediated phagocytosis and inhibits the growth of J774.2. To further evaluate the relationship between cAMP and the specialized functions exhibited by these cells, variants deficient in phagocytosis, adenylate cyclase and cAMP-dependent protein kinase were derived. J774.2 secretes plasminogen activator and this secretion is rapidly and specifically inhibited by 8-bromo-cAMP or cholera toxin under conditions where lysozyme secretion is unaltered. Utilizing protein kinase-deficient variants, the ability of cAMP to inhibit plasminogen activator secretion was mediated by a cAMP-dependent protein kinase. cAMP has diametrically opposing effects on 2 macrophage-like functions: Fc-mediated phagocytosis and plasminogen activator secretion.