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Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2.
J Immunol. 1989 Aug 15; 143(4):1198-205.JI

Abstract

The macrophage-activating properties of murine recombinant granulocyte-macrophage (GM)-CSF were studied in murine peritoneal macrophages with respect to metabolism, endocytosis, PGE2 and TNF-alpha release, and tumor cytotoxicity. GM-CSF was found to be a potent stimulus for RNA and protein synthesis, glucose consumption, pinocytosis, and FcR-independent phagocytosis. Macrophages were activated by GM-CSF to kill TNF-alpha-insensitive Eb lymphoma cells but failed to generate cytotoxicity against TNF-alpha-sensitive L929 cells. Although GM-CSF alone was incapable of stimulating TNF-alpha release, it primed macrophages for elevated TNF-alpha production in response to IFN-gamma plus LPS. The priming effect of GM-CSF disappeared upon longer incubation (greater than 12 h) and was followed by a strongly reduced responsiveness to stimuli that release TNF-alpha. Late-stage suppression could be reverted by treatment with the cyclooxygenase blocker indomethacin, and GM-CSF-induced priming for enhanced TNF-alpha release was entirely restored. The responsible arachidonic acid product mediating suppression was found to be PGE2, because 1) GM-CSF-primed macrophages released enhanced amounts of PGE2 and 2) indomethacin-restored macrophages were again suppressed when exogenous PGE2 was added back in amounts produced by GM-CSF-primed macrophages. Although GM-CSF potently induced TNF-alpha gene transcription by 20 h of treatment, PGE2 interfered with translation into the secreted TNF-alpha protein. These data show that GM-CSF is capable of priming for the enhanced release of two factors, initially for TNF-alpha and subsequently for PGE2. The temporally delayed generation of these two mediators suggests an autoregulatory circuit in which the later produced PGE2 limits GM-CSF-induced macrophage activation.

Authors+Show Affiliations

Institute of Immunology, University of Marburg, West Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2473121

Citation

Heidenreich, S, et al. "Macrophage Activation By Granulocyte/macrophage Colony-stimulating Factor. Priming for Enhanced Release of Tumor Necrosis Factor-alpha and Prostaglandin E2." Journal of Immunology (Baltimore, Md. : 1950), vol. 143, no. 4, 1989, pp. 1198-205.
Heidenreich S, Gong JH, Schmidt A, et al. Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2. J Immunol. 1989;143(4):1198-205.
Heidenreich, S., Gong, J. H., Schmidt, A., Nain, M., & Gemsa, D. (1989). Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2. Journal of Immunology (Baltimore, Md. : 1950), 143(4), 1198-205.
Heidenreich S, et al. Macrophage Activation By Granulocyte/macrophage Colony-stimulating Factor. Priming for Enhanced Release of Tumor Necrosis Factor-alpha and Prostaglandin E2. J Immunol. 1989 Aug 15;143(4):1198-205. PubMed PMID: 2473121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2. AU - Heidenreich,S, AU - Gong,J H, AU - Schmidt,A, AU - Nain,M, AU - Gemsa,D, PY - 1989/8/15/pubmed PY - 1989/8/15/medline PY - 1989/8/15/entrez SP - 1198 EP - 205 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 143 IS - 4 N2 - The macrophage-activating properties of murine recombinant granulocyte-macrophage (GM)-CSF were studied in murine peritoneal macrophages with respect to metabolism, endocytosis, PGE2 and TNF-alpha release, and tumor cytotoxicity. GM-CSF was found to be a potent stimulus for RNA and protein synthesis, glucose consumption, pinocytosis, and FcR-independent phagocytosis. Macrophages were activated by GM-CSF to kill TNF-alpha-insensitive Eb lymphoma cells but failed to generate cytotoxicity against TNF-alpha-sensitive L929 cells. Although GM-CSF alone was incapable of stimulating TNF-alpha release, it primed macrophages for elevated TNF-alpha production in response to IFN-gamma plus LPS. The priming effect of GM-CSF disappeared upon longer incubation (greater than 12 h) and was followed by a strongly reduced responsiveness to stimuli that release TNF-alpha. Late-stage suppression could be reverted by treatment with the cyclooxygenase blocker indomethacin, and GM-CSF-induced priming for enhanced TNF-alpha release was entirely restored. The responsible arachidonic acid product mediating suppression was found to be PGE2, because 1) GM-CSF-primed macrophages released enhanced amounts of PGE2 and 2) indomethacin-restored macrophages were again suppressed when exogenous PGE2 was added back in amounts produced by GM-CSF-primed macrophages. Although GM-CSF potently induced TNF-alpha gene transcription by 20 h of treatment, PGE2 interfered with translation into the secreted TNF-alpha protein. These data show that GM-CSF is capable of priming for the enhanced release of two factors, initially for TNF-alpha and subsequently for PGE2. The temporally delayed generation of these two mediators suggests an autoregulatory circuit in which the later produced PGE2 limits GM-CSF-induced macrophage activation. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/2473121/Macrophage_activation_by_granulocyte/macrophage_colony_stimulating_factor__Priming_for_enhanced_release_of_tumor_necrosis_factor_alpha_and_prostaglandin_E2_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=2473121 DB - PRIME DP - Unbound Medicine ER -