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. Th e signalling for biological effects of this and other cytokines are us ually exerted through cell surface receptors. In this study, we have d emonstrated the presence of a surface TNF alpha receptor type I in mur ine astrocytes of both SJL/J and BALB/c origin, using I-125-labelled r ecombinant mouse TNF alpha. A linear Scatchard plot indicates the pres ence of only one type of receptor with a MW of 58 kDa (Type I TNF rece ptor) 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 ind icate that receptor-bound TNF is rapidly internalized at 37 degrees C and degraded intracellularly to a principal molecular species which el utes from HPLC reverse-phase columns at 38% acetonitrile rather than a t 60%, as native TNF alpha does. The binding is up-regulated by increa sing the number of receptors (but not its affinity) by treatments with Theiler's murine encephalomyelitis virus (TMEV), Con A and inflammato ry cytokines such as IL-1 alpha, IL-6, and INF-gamma. It is not influe nced by vaccinia virus, IL-2, or LPS. This receptor may contribute to the initiation of perpetuation of the immune response which mediates t he demyelinating inflammation induced by Theiler's virus. (C) 1995 Wil ey-Liss, Inc.