Steeg P S, Johnson H M, Oppenheim J J
J Immunol. 1982 Dec;129(6):2402-6.
The initiation of antigen-specific, T-dependent immune responses by macrophages requires their expression of Ia antigens. Ia antigen-deficient (Ia-) peritoneal exudate or P388D1 cell line macrophages, when incubated for 2 to 3 days with partially purified immune interferon (IFN-gamma), expressed Ia antigen, as detected by antibody-and-complement-mediated cytotoxicity. This paper reports that bacterial endotoxin (lipopolysaccharide, LPS) inhibited both IFN-gamma induction of macrophage Ia antigen expression and IFN maintenance of the Ia+ state in a dose-dependent manner. In the absence of IFN-gamma, LPS had no significant effect on macrophage Ia antigen expression. The inhibitory effects of LPS were abrogated by the addition of indomethacin into the culture medium. Further, 10(-10) to 10(-6) M exogenous prostaglandin E2 or 10(-6) to 10(-4) M exogenous dibutryl 3'5' cyclic adenosine monophosphate also inhibited IFN-gamma regulation of macrophage Ia antigen expression. The data suggest that LPS inhibits IFN-gamma regulation of macrophage Ia antigen expression by stimulating macrophage prostaglandin E2 production, and consequently enhancing intracellular cAMP levels. The data outline an inhibitory pathway involved in the regulation of macrophage Ia antigen expression, and may explain, in part, reported immunosuppressive effects of LPS.
巨噬细胞引发抗原特异性、T 细胞依赖性免疫反应需要其表达 Ia 抗原。Ia 抗原缺陷（Ia-）的腹腔渗出液或 P388D1 细胞系巨噬细胞，与部分纯化的免疫干扰素（IFN-γ）一起孵育 2 至 3 天时，通过抗体和补体介导的细胞毒性检测发现其表达了 Ia 抗原。本文报道细菌内毒素（脂多糖，LPS）以剂量依赖性方式抑制巨噬细胞 Ia 抗原表达的 IFN-γ诱导以及 Ia+状态的 IFN 维持。在没有 IFN-γ的情况下，LPS 对巨噬细胞 Ia 抗原表达没有显著影响。向培养基中添加吲哚美辛可消除 LPS 的抑制作用。此外，10（-10）至 10（-6）M 的外源性前列腺素 E2 或 10（-6）至 10（-4）M 的外源性二丁酰 3',5'-环磷酸腺苷也抑制巨噬细胞 Ia 抗原表达的 IFN-γ调节。数据表明 LPS 通过刺激巨噬细胞前列腺素 E2 的产生，进而提高细胞内 cAMP 水平，来抑制巨噬细胞 Ia 抗原表达的 IFN-γ调节。这些数据概述了一条参与巨噬细胞 Ia 抗原表达调节的抑制途径，并且可能部分解释了报道的 LPS 的免疫抑制作用。
