Cytolysis of adenovirus-infected murine fibroblasts by IFN-gamma-primed macrophages is TNF- and contact-dependent.
The effect of interferon-gamma (IFN-gamma) priming on macrophages for cytolysis of adenovirus-infected murine fibroblasts was examined using peritoneal macrophages and the RAW264.7 (RAW) murine macrophage cell line. Adenovirus-infected cells were lysed by IFN-gamma-primed RAW macrophages via a TNF- and contact-dependent mechanism under conditions in which little or no soluble TNF was detected in the supernatant of these effectors. TNF involvement in the lytic mechanism of IFN-gamma-primed macrophages is shown by (a) cytolysis of TNF-sensitive LM and adenovirus E1A-expressing cells, (b) protection from cytolysis by the adenovirus E3-14.7K protein and the E3-10.4/14.5K complex of proteins, and (c) inhibition of cytolysis when neutralizing anti-TNF serum is added to cocultures of macrophages and susceptible adenovirus-infected targets. Physical separation of effectors and targets prevents cytolysis, indicating that cell contact is required. Nonetheless, IFN-gamma-primed RAW macrophages are unable to lyse E8 tumor cells, which are killed by fully activated (triggered) macrophages. These findings indicate that IFN-gamma-primed macrophages are cytolytic for TNF-sensitive targets without soluble TNF release, but they lack the full cytolytic capacity of LPS-triggered macrophages.
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322.
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D016475:3T3 Cells; D000256:Adenoviridae / Q000276:immunology*; D017500:Adenovirus E1A Proteins / Q000276:immunology*; D017503:Adenovirus E3 Proteins / Q000276:immunology; D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic; D005814:Genes, Viral; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D013539:Simian virus 40 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D017500:Adenovirus E1A Proteins; D017503:Adenovirus E3 Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma