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

We identified recently an endogenous murine leukemia virus (MuLV) envelope protein as a new autoantigen reactive with autoimmune diabetic mouse sera a nd observed immunosuppressive activity of this envelope protein. In the pre sent study, to elucidate the mechanism involved, we treated macrophages wit h the envelope protein and investigated activation of macrophage. We found enhancements of NOS mRNA and nitrite in envelope protein-treated RAW264.7 c ells and peritoneal macrophages. The stimulation was highly envelope protei n-specific, and also time- and dose-dependent. The activation pattern was s imilar to that elicited by lipopolysaccharide (LPS) since the envelope prot ein showed a synergistic effect on macrophage activation in conjunction wit h interferon gamma (IFN-gamma). Furthermore, deacylated LPS as a competitiv e inhibitor of LPS showed inhibition of envelope protein-mediated macrophag e activation. These data show that MuLV envelope protein can be a new macro phage activator and suggest that the retroviral envelope protein may elicit immunosuppressive activity through macrophage activation. (C) 2001 Elsevie r Science B.V. All rights reserved.