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PMID:8387893
| Citation |
Pfeffer, K, Matsuyama, T, Kündig, TM, Wakeham, A, Kishihara, K, Shahinian, A, Wiegmann, K, Ohashi, PS, Krönke, M and Mak, TW (1993) Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73:457-67 |
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| Abstract |
The multiple biological activities of tumor necrosis factor (TNF) are mediated by two distinct cell surface receptors of 55 kd (TNFRp55) and 75 kd (TNFRp75). Using gene targeting, we generated a TNFRp55-deficient mouse strain. Cells from TNFRp55-/-mutant mice lack expression of TNFRp55 but display normal numbers of high affinity TNFRp75 molecules. Thymocyte development and lymphocyte populations are unaltered, and clonal deletion of potentially self-reactive T cells is not impaired. However, TNF signaling is largely abolished, as judged by the failure of TNF to induce NF-kappa B in T lymphocytes from TNFRp55-deficient mice. The loss of TNFRp55 function renders mice resistant to lethal dosages of either lipopolysaccharides or S. aureus enterotoxin B. In contrast, TNFRp55-deficient mice are severely impaired to clear L. monocytogenes and readily succumb to infection. Thus, the 55 kd TNFR plays a decisive role in the host's defense against microorganisms and their pathogenic factors. |
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| Keywords |
Animals; Base Sequence; Cell Nucleus/metabolism; Cloning, Molecular; Humans; Immunity, Innate/genetics; Kinetics; Lipopolysaccharides/toxicity; Listeriosis/immunology; Listeriosis/physiopathology; Liver/pathology; Lymphocytes/metabolism; Mice; Mice, Mutant Strains; Molecular Sequence Data; Molecular Weight; NF-kappa B/metabolism; Oligodeoxyribonucleotides; Polymerase Chain Reaction/methods; Radioligand Assay; Receptors, Cell Surface/chemistry; Receptors, Cell Surface/genetics; Receptors, Cell Surface/metabolism; Receptors, Tumor Necrosis Factor; Shock, Septic/immunology; Shock, Septic/pathology; Transfection; Tumor Necrosis Factor-alpha/metabolism; Tumor Necrosis Factor-alpha/pharmacology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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