Combined effects of tumor necrosis factor-alpha, prostaglandin E2, and corticosterone on induced Ia expression on murine macrophages.
Ia expression is an important marker of macrophage functional capacity. IFN-gamma induces Ia expression on perhaps all murine macrophages, whereas IL-4, granulocyte-macrophage CSF, and CSF-1 induce Ia on restricted sets of macrophages. Inhibitors of expression include PGE2, glucocorticoids, and IFN-beta. TNF has been found to augment Ia expression on several macrophage lineage cell lines but to inhibit expression on murine peritoneal macrophages. Our study shows that TNF can have opposite effects on Ia expression (induced by IFN-gamma) on thioglycollate-elicited peritoneal macrophages, depending on the length of time cells are treated and on the presence of other modulators. In particular, TNF augmented early expression induced by IFN-gamma but inhibited later expression. And although TNF synergized with PGE2 to markedly inhibit Ia induction on these cells, it partially antagonized the inhibition by corticosterone and IFN-beta. TNF and PGE2 also synergized to inhibit Ia expression induced on bone marrow-derived and splenic macrophages by either IFN-gamma or IL-4. In contrast to their effect on Ia expression, TNF and PGE2 had opposite effects on expression of gamma 2a FcR in macrophages. TNF blocked the increase in FcR expression due to any combination of PGE2, IFN-gamma, and IFN-beta. However, TNF and PGE2 both increased expression of gamma 2a FcR on WEHI-3 cells. If the different effects of TNF reflect the differentiation states of macrophages, its effects on Ia and FcR expression may vary with the progression of an immune response.
Zimmer
T
T
Department of Biological Sciences, Stanford University, CA 94305.
Jones
P P
PP
D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D011961:Receptors, Fc / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000949:Histocompatibility Antigens Class II; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015232:Dinoprostone; D003345:Corticosterone