Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors.

Research output: Contribution to journalJournal articleResearchpeer-review

D Aderka, H Engelmann, Y Maor, C Brakebusch, D Wallach

The receptors for tumor necrosis factor (TNF) exist in cell-associated as well as soluble forms, both binding specifically to TNF. Since the soluble forms of TNF receptors (sTNF-Rs) can compete with the cell-associated TNF receptors for TNF, it was suggested that they function as inhibitors of TNF activity; at high concentrations, the sTNF-Rs indeed inhibit TNF effects. However, we report here that in the presence of low concentrations of the sTNF-Rs, effects of TNF whose induction depend on prolonged treatment with this cytokine are augmented, reflecting an attenuation by the sTNF-Rs of spontaneous TNF activity decay. Evidence that this stabilization of TNF activity by the sTNF-Rs follows from stabilization of TNF structure within the complexes that TNF forms with the sTNF-Rs is presented here, suggesting that the sTNF-Rs can affect TNF activity not only by interfering with its binding to cells but also by stabilizing its structure and preserving its activity, thus augmenting some of its effects.
Original languageEnglish
JournalJournal of Experimental Medicine
Volume175
Issue number2
Pages (from-to)323-9
Number of pages6
ISSN0022-1007
Publication statusPublished - 1992

Bibliographical note

Keywords: Cell Count; Cells, Cultured; Chromatography, Gel; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Humans; Kinetics; Leukemia, Lymphocytic, Chronic, B-Cell; Receptors, Cell Surface; Receptors, Tumor Necrosis Factor; Recombinant Proteins; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

ID: 5160452