The receptor for tumor necrosis factor on murine astrocytes: Characterization, intracellular degradation, and regulation by cytokines and theiler's murine encephalomyelitis virus

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Abstract
Previous reports have shown that tumor necrosis factor (TNF) exerts a role on the physiology of astrocytes under inflammatory situations. The signalling for biological effects of this and other cytokines are usually exerted through cell surface receptors. In this study, we have demonstrated the presence of a surface TNF α receptor type I in murine astrocytes of both SJL/J and BALB/c origin, using 125I‐labelled recombi‐nant mouse TNFα. A linear Scatchard plot indicates the presence of only one type of receptor with a MW of 58 kDa (Type I TNF receptor) that binds the ligand with a Kd of 1 10−9 M. There are 3,000 copies of this receptor on untreated astrocytes. The results also indicate that receptor‐bound TNF is rapidly internalized at 37°C and degraded intracellularly to a principal molecular species which elutes from HPLC reverse‐phase columns at 38% acetonitrile rather than at 60% as native TNFα does. The binding is up‐regulated by increasing the number of receptors (but not its affinity) by treatments with Theiler's murine encephalomyelitis virus (TMEV), Con A and inflammatory cyto‐kines such as IL‐1, IL‐6 and INF‐β. It is not influnced by vaccinia virus, IL‐2, or LPS. This receptor may contribute to the initiation of perpetuation of the immune response which mediates the demyelinating inflammation induced by Theiler's virus.