Effects of retinoids on macrophage function and IL-1 activity.
The effects of three retinoids, all-trans-retinoic acid (RA), 13-cis-retinoic acid (cRA), and N-(4-hydroxyphenyl) retinamide (4-HPR), on macrophage function were evaluated. In vitro, RA, cRA, and 4-HPR caused a greater than twofold increase in phagocytosis of IgG-sensitized bovine erythrocytes (IgG-ORBC) by a mouse macrophage cell line (RAW). Significant increases in phagocytosis were produced by retinoid concentrations as low as 2 x 10(-10) M. RA also significantly increased phagocytosis of IgG-sensitized ORBC by BALB/c peritoneal macrophages in vitro. The ability of RAW macrophages to bind IgG-ORBC was significantly increased by 10(-6) to 10(-14) M RA. The potentiation of mitogenic responses of spleen cells to Con A and PWM by RA was relatively independent of macrophage function, i.e., splenocytes that were macrophage-depleted were responsive to the potentiating effects of RA. The effects of retinoids on T-cell-dependent B-cell mitogenesis induced by PWM appeared not to be dependent on their previously reported capacity to alter prostaglandin synthesis. Treatment of spleen cells with 10(-6) M indomethacin did not abolish the potentiating effects of RA. However, RA in a dose-dependent fashion increased IL-1 activity at the level of the target T-cell. The greatest potentiation of IL-1 activity was at 10(-8) M RA. These results show that retinoids can modulate macrophage function at two different levels: potentiation of phagocytosis and potentiation of IL-1 activity at the level of the T-cell.
Dillehay
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DL
Birmingham Veterans Administration Hospital, AL 35294.
Walia
A S
AS
Lamon
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EW
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D005260:Female; D007375:Interleukin-1 / Q000032:analysis*; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008934:Mitogens / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D012176:Retinoids / Q000494:pharmacology*
D000943:Antigens, Differentiation; D007375:Interleukin-1; D008934:Mitogens; D011961:Receptors, Fc; D017452:Receptors, IgG; D012176:Retinoids