title: Temporally different stimulation of TNF-alpha and PGE2 release from GM-CSF-primed macrophages.
abstract: Since granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously been shown to activate macrophages, it was of particular interest to study its effect on synthesis and release of tumor necrosis factor-alpha (TNF-alpha). GM-CSF alone was incapable of activating murine peritoneal macrophages to TNF-alpha release. However, in response to lipopolysaccharide (LPS), GM-CSF was found to prime macrophages for enhanced TNF-alpha production. This priming effect was short-lived and was superseded by the contrary, an unresponsiveness to LPS. The suppressed response was due to a delayed production of prostaglandin E2 (PGE2) which did not affect GM-CSF-enhanced TNF-alpha gene transcription but blocked TNF-alpha production. When PGE2 synthesis was inhibited by indomethacin, the priming effect of GM-CSF was entirely reconstituted. Thus, GM-CSF initially primes for TNF-alpha and subsequently for PGE2 release which, taken together, may represent an autoregulatory feed-back system that could restrict macrophage activation.
authors.affiliation: Institute of Immunology, Philipps University, Marburg, FRG.
authors.forename: S
authors.initials: S
authors.lastname: Heidenreich
authors.forename: J H
authors.initials: JH
authors.lastname: Gong
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: M
authors.initials: M
authors.lastname: Nain
authors.forename: D
authors.initials: D
authors.lastname: Gemsa
mesh_terms: D000818:Animals; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D003115:Colony-Stimulating Factors; D006133:Growth Substances; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015232:Dinoprostone