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Mononuclear phagocytes: responders to and producers of interferon
Abstract:
We have provided evidence that in vivo-induced type I IF enhanced Fc-mediated particle uptake by mouse macrophages. Fc-mediated phagocytosis of opsonized erythrocytes by unelicited fresh or cultivated macrophages was stimulated by 4-8 hours of cultivation with 100 ohms/ml IF. A 1-hour pulse was sufficient when followed by incubation in If-free medium. Pactamycin, a protein synthesis inhibitor, and camptothecin, and RNA synthesis inhibitor, blocked the stimulation of phagocytosis, indicating a requirement for macromolecular synthesis. Binding by the macrophages of a radioiodinated monoclonal antibody with anti-Fc receptor II specificity indicated that the stimulation of phagocytosis did not result from an increase in the numbers of available Fc receptors. Inflammatory macrophages, while more phagocytic than resting cells, could be further stimulated by IF in vitro, as could macrophages stimulated with LPS. In contrast, macrophages obtained from animals treated with IF inducers could not be further stimulated by IF. LPS-prestimulated and normal macrophages showed similar time-course and dose-response curves to IF, indicating that the probable mechanism of stimulation is similar in both types of cells. Cultivated bone marrow-derived macrophages found to be sensitive to IF induction by LPS, poly I.C., or NDV. The induction of IF by either LPS or poly I.C. was greater at 26 degrees C than at 37 degrees C, while no such difference was found using NDV. A 2-hour pulse of LPS was sufficient to induce IF in marrow-derived macrophages. The induced IF activity was shown to be type I IF.
Insights
Type I interferon (IF) enhances macrophage phagocytosis by increasing Fc-mediated particle uptake. This process requires new protein and RNA synthesis but does not involve increased Fc receptors.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages play a crucial role in the immune system through phagocytosis.
- Interferons (IFs) are known modulators of immune responses.
Purpose of the Study:
- To investigate the effect of type I interferon (IF) on Fc-mediated phagocytosis by mouse macrophages.
- To elucidate the mechanism by which IF enhances phagocytosis.
Main Methods:
- Cultivation of mouse macrophages with type I IF.
- Assessing Fc-mediated phagocytosis of opsonized erythrocytes.
- Inhibition studies using protein and RNA synthesis inhibitors.
- Analysis of Fc receptor expression using anti-Fc receptor II antibodies.
- Stimulation of macrophages with lipopolysaccharide (LPS) and IF inducers.
Main Results:
- In vivo-induced type I IF significantly enhanced Fc-mediated particle uptake by macrophages.
- IF stimulation of phagocytosis required 4-8 hours of cultivation and depended on macromolecular synthesis.
- The enhancement of phagocytosis was not due to an increase in Fc receptor numbers.
- Inflammatory and LPS-stimulated macrophages could be further enhanced by IF.
- Macrophage-derived IF induction by LPS or poly I:C was more efficient at 26°C than 37°C.
Conclusions:
- Type I IF is a potent stimulator of Fc-mediated phagocytosis in macrophages.
- The mechanism involves de novo synthesis of molecules, not increased Fc receptor expression.
- IF can further enhance the phagocytic capacity of inflammatory and LPS-primed macrophages.