The TNF receptor in TNF-mediated cytotoxicity.
The in vitro cytotoxic capacity (if not every pleiotropic property) of tumor necrosis factor (TNF) begins by interaction with specific high affinity cell surface receptors. The characterization of receptors and ligand kinetics is reviewed in relationship to cytotoxicity. Decreased receptor number and affinity correlate with sensitivity within a given cell line. In L-M cells (a sensitive tumorigenic fibroblast), TNF induces a biphasic downregulation of receptors. Internalized ligand and receptors are largely cleared before the onset of cell death. Drugs affecting cytotoxicity may act primarily on an early 'association' stage (ligand receptor interaction, internalization or perhaps signal transduction) or on a later 'lytic' stage. Phorbol myristate acetate is an example of the former, while chloroquine, cholera toxin and dibutyryl cyclic AMP are examples of the latter.
Kull
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FC
Molecular Biology Department, Burroughs Wellcome Co., Research Triangle Park, N.C.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003994:Bucladesine; D013755:Tetradecanoylphorbol Acetate