Cytokine Priming Reduces Dependence on TNF-R2 for TNF-α-Mediated Induction of Macrophage Nitric Oxide Generation
Document Type
Article
Publication Date
1-1-1996
Description
In the presence of interferon-γ, (IFN-γ), human tumor necrosis factor- α (Hu-TNF-α), which binds to murine TNF-α receptor type 1 (TNF-R1) but not to murine TNF-R2, was effective in inducing nitric oxide (NO) production in spleen-derived macrophages (Mφ), albeit at concentrations 12.5-fold greater than those required by murine TNF-α (Mu-TNF-α), to achieve the same result. Addition of anti-TNF-R1 completely inhibited the Mu-TNF-α-mediated induction of NO, demonstrating that TNF-R1 is critical to the IFN-γ-dependent TNF-α- mediated induction of Mφ effector function. However, treatment with anti- TNF-R2 resulted in a partial inhibition of Mφ activation. Spleen-derived Mφ were more dependent on TNF-R2 than RAW 264.7 or peritoneal Mφ based on their responsiveness to Hu-TNF-α. Priming of spleen-derived Mφ with either IFN- γ or granulocyte-macrophage colony-stimulating factor (GM-CSF) heightened the maximal responses to both TNF-a species and increased the overall effectiveness of Hu-TNF-α without increasing expression of either TNF-a receptor. The dependence of spleen-derived Mφ on both TNF-α receptors for signaling the induction of effector function supports an active signaling role for TNF-R2 in its synergy with TNF-R1 rather than a passive ligand passing role.
Citation Information
Miller, Annette R.; Suttles, Jill; and Stout, Robert D.. 1996. Cytokine Priming Reduces Dependence on TNF-R2 for TNF-α-Mediated Induction of Macrophage Nitric Oxide Generation. Journal of Interferon and Cytokine Research. Vol.16(12). 1055-1063. https://doi.org/10.1089/jir.1996.16.1055 PMID: 8974009 ISSN: 1079-9907