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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 mediated phagocytosis, antibody mediated cytotoxicity, chemotaxis, and lysozyme secretion. Cyclic AMP stimulates Fc-mediated phagocytosis and inhibits the growth of J774.2. To further evaluate the relationship between cyclic AMP and the specialized functions exhibited by these cells. Variants deficient in phagocytosis, adenylate cyclase and cyclic AMP-dependent protein kinase were derived. We have now shown that J774.2 also secretes plasminogen activator and that this secretion is rapidly and specifically inhibited by 8-bromoadenosine 3':5'-cyclic monophosphoric acid (8 Br--cAMP) or cholera toxin under conditions where lysozyme secretion is unaltered. Utilizing protein kinase-deficient variants, the ability of cyclic AMP to inhibit plasminogen activator secretion was shown to be mediated by a cyclic AMP-dependent protein kinase. We conclude that cyclic AMP has diametrically opposing effects on two macrophage-like functions: Fc-mediated phagocytosis and plasminogen activator secretion.
Insights
Cyclic adenosine monophosphate (cAMP) has opposing effects on macrophage-like J774.2 cells. It stimulates Fc-mediated phagocytosis while inhibiting plasminogen activator secretion via a protein kinase pathway.
Area of Science:
- Immunology
- Cell Biology
Background:
- The J774.2 cell line possesses macrophage-like functions, including phagocytosis and secretion.
- Cyclic adenosine monophosphate (cAMP) is known to stimulate Fc-mediated phagocytosis and inhibit J774.2 cell growth.
Purpose of the Study:
- To investigate the relationship between cAMP and specialized functions in J774.2 cells.
- To determine the role of cAMP in regulating plasminogen activator secretion.
Main Methods:
- Derivation of J774.2 variants deficient in phagocytosis, adenylate cyclase, and cAMP-dependent protein kinase.
- Treatment with 8-bromoadenosine 3':5'-cyclic monophosphoric acid (8-Br-cAMP) and cholera toxin to assess effects on secretion.
- Evaluation of plasminogen activator and lysozyme secretion under various conditions.
Main Results:
- Cyclic AMP (cAMP) stimulates Fc-mediated phagocytosis in J774.2 cells.
- cAMP rapidly and specifically inhibits plasminogen activator secretion, an effect mediated by cAMP-dependent protein kinase.
- Lysozyme secretion remains unaltered under conditions affecting plasminogen activator secretion.
Conclusions:
- Cyclic AMP exhibits opposing regulatory effects on distinct macrophage-like functions.
- Fc-mediated phagocytosis is stimulated by cAMP, whereas plasminogen activator secretion is inhibited.