Haddad E K, Duclos A J, Antecka E, Lapp W S, Baines M G
Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
Cell Immunol. 1997 Oct 10;181(1):68-75. doi: 10.1006/cimm.1997.1199.
We have previously shown that both priming and triggering signals were needed for nitric oxide production by decidual macrophages and that nitric oxide was responsible for embryo wastage. In this study, we investigated the role of IFN-gamma as the primary signal for macrophage activation in early embryo loss. IFN-gamma-deficient (GKO) and heterozygous F1 control mice were injected with lipopolysaccharide (LPS) at day 7 of gestation. The results showed that the GKO mice were more resistant to LPS-induced embryo loss than the wild type. This suggested that IFN-gamma was needed for LPS-induced embryo resorption and that decidual macrophages from pregnant GKO mice were not primed and could not be activated when given LPS. Further, the results showed that IFN-gamma mRNA was simultaneously expressed in the same embryos that also expressed mRNA markers for macrophage activation (TNF-alpha and iNOS), indicating that macrophage activation could be a consequence of IFN-gamma production. Similarly, we investigated the role of IL-12 as a switch cytokine capable of eliciting TH1-associated cytokine production including IFN-gamma. The results showed that IL-12 mRNA expression was correlated with IFN-gamma expression and macrophage activation. In this in vivo study, we showed for the first time that spontaneously increased decidual IFN-gamma expression is detrimental to embryo survival.
我们之前已经表明，蜕膜巨噬细胞产生一氧化氮既需要启动信号也需要触发信号，并且一氧化氮是胚胎丢失的原因。在本研究中，我们调查了γ干扰素作为早期胚胎丢失中巨噬细胞激活的主要信号的作用。在妊娠第7天给γ干扰素缺陷（GKO）小鼠和杂合子F1对照小鼠注射脂多糖（LPS）。结果显示，GKO小鼠比野生型小鼠对LPS诱导的胚胎丢失更具抵抗力。这表明LPS诱导的胚胎吸收需要γ干扰素，并且来自怀孕GKO小鼠的蜕膜巨噬细胞未被启动，给予LPS时不能被激活。此外，结果显示γ干扰素mRNA在同时也表达巨噬细胞激活的mRNA标志物（肿瘤坏死因子-α和诱导型一氧化氮合酶）的相同胚胎中同时表达，表明巨噬细胞激活可能是γ干扰素产生的结果。同样，我们调查了白细胞介素-12作为一种能够引发包括γ干扰素在内的与TH1相关的细胞因子产生的转换细胞因子的作用。结果显示白细胞介素-12 mRNA表达与γ干扰素表达和巨噬细胞激活相关。在这项体内研究中，我们首次表明蜕膜γ干扰素表达的自发增加对胚胎存活有害。
