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Activation of mouse macrophage by soluble endogenous murine leukemia virus (MuLV) envelope protein
1Laboratory of Endocrinology, Institute for Medical Sciences, Ajou University School of Medicine, Wonchon-dong san5, Paldal-gu, Sowon, 442-749, Kyunggi-Do, South Korea.
Abstract:
We identified recently an endogenous murine leukemia virus (MuLV) envelope protein as a new autoantigen reactive with autoimmune diabetic mouse sera and observed immunosuppressive activity of this envelope protein. In the present study, to elucidate the mechanism involved, we treated macrophages with the envelope protein and investigated activation of macrophage. We found enhancements of iNOS mRNA and nitrite in envelope protein-treated RAW264.7 cells and peritoneal macrophages. The stimulation was highly envelope protein-specific, and also time- and dose-dependent. The activation pattern was similar to that elicited by lipopolysaccharide (LPS) since the envelope protein showed a synergistic effect on macrophage activation in conjunction with interferon gamma (IFN-gamma). Furthermore, deacylated LPS as a competitive inhibitor of LPS showed inhibition of envelope protein-mediated macrophage activation. These data show that MuLV envelope protein can be a new macrophage activator and suggest that the retroviral envelope protein may elicit immunosuppressive activity through macrophage activation.
Insights
Murine leukemia virus (MuLV) envelope protein activates macrophages, potentially explaining its immunosuppressive effects. This retroviral protein acts as a novel macrophage activator, influencing immune responses.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Endogenous murine leukemia virus (MuLV) envelope protein identified as an autoantigen in diabetic mouse sera.
- MuLV envelope protein exhibits immunosuppressive activity, prompting investigation into its mechanism.
Purpose of the Study:
- To elucidate the mechanism behind the immunosuppressive activity of MuLV envelope protein.
- To investigate the activation of macrophages by MuLV envelope protein.
Main Methods:
- Macrophages (RAW264.7 cell line and peritoneal macrophages) were treated with MuLV envelope protein.
- Levels of inducible nitric oxide synthase (iNOS) mRNA and nitrite were measured.
- Macrophage activation was assessed in conjunction with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS).
- Competitive inhibition assays using deacylated LPS were performed.
Main Results:
- MuLV envelope protein treatment enhanced iNOS mRNA and nitrite levels in macrophages.
- The observed macrophage activation was specific to the envelope protein and demonstrated time- and dose-dependency.
- MuLV envelope protein showed synergistic effects on macrophage activation with IFN-gamma.
- Deacylated LPS inhibited envelope protein-mediated macrophage activation, suggesting an LPS-like signaling pathway.
Conclusions:
- MuLV envelope protein functions as a novel macrophage activator.
- Macrophage activation by MuLV envelope protein may mediate its observed immunosuppressive activity.
- Retroviral envelope proteins could play a role in immune modulation through macrophage activation.