Activation of mouse macrophage by soluble endogenous murine leukemia virus (MuLV) envelope protein

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-γ). 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.