Related Experiment Videos
Effect of aging on murine macrophages. Diminished response to IFN-gamma for enhanced oxidative metabolism
1Department of Medicine, Cornell University Medical College, New York, NY 10021.
Abstract:
The ability of macrophages to secrete reactive oxygen intermediates, as well as reactive nitrogen intermediates, correlates closely with their capacity to perform two critical effector functions: intracellular killing of microorganisms and lysis of tumor cells. In this study, age-associated changes in the ability of caseinate-elicited peritoneal macrophages to release hydrogen peroxide were determined. Macrophages from aged BALB/c mice produced 50% less hydrogen peroxide than those from young mice in response to PMA or opsonized zymosan. In contrast, the production of macrophage-activating cytokines including IFN-gamma was not diminished in splenocyte supernatants from the aged group. Furthermore, no difference was detected in surface expression of IFN-gamma receptor in old and young mice. Macrophage responses to IFN-gamma, however, declined with aging. In vitro, IFN-gamma-induced release of hydrogen peroxide and nitric oxide was 50% lower in old mice than in young mice. IFN-gamma-induced tyrosine phosphorylation of MAPK, an early activation event, was undetectable in macrophages from the aged mice. These data demonstrate that diminished responses of macrophages to activating signals are one aspect of the impaired immune response in aged mice.
Insights
Aging impairs macrophage immune function. Aged mice show reduced hydrogen peroxide release and diminished responses to activating signals like interferon-gamma (IFN-γ), indicating an aged immune response.
Area of Science:
- Immunology
- Cellular Biology
- Aging Research
Background:
- Macrophages are crucial immune cells involved in pathogen killing and tumor surveillance.
- Their effector functions rely on the secretion of reactive oxygen and nitrogen intermediates.
- Aging is associated with a decline in immune system efficiency.
Purpose of the Study:
- To investigate age-associated changes in the hydrogen peroxide (H2O2) release capacity of macrophages.
- To determine the impact of aging on macrophage responses to activating cytokines, specifically interferon-gamma (IFN-γ).
Main Methods:
- Caseinate-elicited peritoneal macrophages were isolated from young and aged BALB/c mice.
- Hydrogen peroxide production was measured in response to phorbol 12-myristate 13-acetate (PMA) and opsonized zymosan.
- Splenocyte supernatants were analyzed for macrophage-activating cytokines like IFN-γ.
- Surface expression of the IFN-γ receptor was assessed.
- In vitro studies evaluated IFN-γ-induced H2O2 and nitric oxide release and MAPK phosphorylation.
Main Results:
- Macrophages from aged mice produced 50% less H2O2 compared to young mice.
- IFN-γ production by splenocytes was not diminished in aged mice.
- No difference in IFN-γ receptor surface expression was observed between age groups.
- In vitro, IFN-γ-induced H2O2 and nitric oxide release was 50% lower in aged mice.
- IFN-γ-induced MAPK phosphorylation was undetectable in macrophages from aged mice.
Conclusions:
- Diminished macrophage responsiveness to activating signals contributes to the impaired immune response in aged mice.
- Aging affects the intracellular signaling pathways crucial for macrophage effector functions.
- These findings highlight a cellular basis for age-related immune dysfunction.