THE RECEPTOR FOR TUMOR-NECROSIS-FACTOR ON MURINE ASTROCYTES - CHARACTERIZATION, INTRACELLULAR DEGRADATION, AND REGULATION BY CYTOKINES AND THEILERS MURINE ENCEPHALOMYELITIS VIRUS

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 alpha receptor type I in murine astrocytes of both SJL/J and BALB/c origin, using I-125-labelled recombinant mouse TNF alpha. 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 x 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 degrees 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 TNF alpha 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 cytokines such as IL-1 alpha, IL-6, and INF-gamma. It is not influenced 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. (C) 1995 Wiley-Liss, Inc.