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Modulation of mouse peritoneal macrophage Ia and human peritoneal macrophage HLA-DR expression by alpha
Abstract:
alpha 2-Macroglobulin (alpha 2M) is converted from its native form into electrophoretically "fast" forms by reaction with proteinases or with methylamine. The "fast" forms both bind to specific receptors on macrophages (MP). We have previously shown that alpha 2M "fast" forms modulate effector functions of murine peritoneal MP. In the present study, alpha 2M "fast" forms antagonized the increase in MP HLA-DR and Ia expression induced in vitro by interferon-gamma (IFN-gamma). This effect was observed with human peritoneal MP, as well as MP from peptone-injected and bacillus Calmette-Guérin-infected mice of three strains. alpha 2M-trypsin, which had been reacted with aprotinin and alpha 2M-methylamine, both of which lack proteolytic activity, also antagonized interferon-induced Ia expression. alpha 2M "fast" forms also reduced the ability of MP to serve as accessory cells for lectin-induced lymphocyte proliferation. alpha 2M "fast" form is an immune modulator of human and murine MP function, probably through a specific receptor-mediated mechanism.
Insights
Alpha 2-Macroglobulin (alpha 2M) fast forms act as immune modulators. These modified alpha 2M forms can suppress macrophage responses to interferon-gamma and reduce their ability to stimulate lymphocyte proliferation.
Area of Science:
- Immunology
- Biochemistry
- Cell Biology
Background:
- Alpha 2-Macroglobulin (alpha 2M) undergoes conformational changes to "fast" forms upon reaction with proteinases or methylamine.
- These "fast" alpha 2M forms bind to specific macrophage (MP) receptors.
- Previous research indicated alpha 2M "fast" forms modulate murine peritoneal MP effector functions.
Purpose of the Study:
- To investigate the immunomodulatory effects of alpha 2M "fast" forms on human and murine macrophages.
- To determine if alpha 2M "fast" forms antagonize interferon-gamma (IFN-gamma)-induced changes in MP.
- To assess the impact of alpha 2M "fast" forms on MP accessory cell function.
Main Methods:
- In vitro studies using human peritoneal MP and MP from various mouse models (peptone-injected, bacillus Calmette-Guérin-infected).
- Assessing MP HLA-DR and Ia expression following IFN-gamma stimulation in the presence of alpha 2M "fast" forms.
- Evaluating the effect of alpha 2M "fast" forms (including proteolytically inactive variants) on IFN-gamma-induced Ia expression.
- Measuring the capacity of MP to act as accessory cells in lectin-induced lymphocyte proliferation assays.
Main Results:
- Alpha 2-Macroglobulin "fast" forms antagonized IFN-gamma-induced increases in MP HLA-DR and Ia expression in both human and murine MP.
- This inhibitory effect was observed with proteolytically inactive alpha 2M "fast" forms (alpha 2M-trypsin reacted with aprotinin, and alpha 2M-methylamine).
- Alpha 2-Macroglobulin "fast" forms reduced the ability of MP to serve as accessory cells for lymphocyte proliferation.
Conclusions:
- Alpha 2-Macroglobulin "fast" forms function as immune modulators for both human and murine MP.
- The immunomodulatory mechanism likely involves specific receptor-mediated interactions.
- These findings highlight a novel role for modified alpha 2M in regulating immune cell function.