Clark D A, Chaouat G, Arck P C, Mittruecker H W, Levy G A
McMaster University, Hamilton, Ontario, Canada.
J Immunol. 1998 Jan 15;160(2):545-9.
Spontaneous resorption in the CBA x DBA/2 model is attributed to NK cells, macrophages, and Th1-type cytokines. In vivo depletion of NK cells by anti-asialoGM1 Ab or macrophage depletion by silicon dioxide treatment reduced abortion rates, which could no longer be boosted by injecting TNF-alpha (which activates NK cells) or IFN-gamma (which activates macrophages). TNF-alpha + gamma-IFN coadministration aborted >80% of the embryos whether or not NK cells or macrophages had been depleted or estradiol + progesterone was injected to correct potential reduction in ovarian function by cytokines. The cytokines also aborted IRF1+/+ C57BL/6 but not IRF1-/- females pregnant by IRF1+/+ DBA/2. Both spontaneous and cytokine-boosted abortions in CBA x DBA/2 were blocked by Ab to fgl2 prothrombinase [corrected] expressed by cytokine-stimulated vascular endothelial cells and monocytes; in vivo Ab depletion of granulocytes also prevented TNF-alpha + IFN-gamma-induced abortions. Cytokine-triggered thrombotic/inflammatory processes in maternal uteroplacental blood vessels causes abortion.
在CBA×DBA/2模型中，自然吸收归因于自然杀伤细胞、巨噬细胞和Th1型细胞因子。用抗唾液酸GM1抗体在体内清除自然杀伤细胞或用二氧化硅处理清除巨噬细胞可降低流产率，注射肿瘤坏死因子-α（激活自然杀伤细胞）或干扰素-γ（激活巨噬细胞）后流产率不再升高。无论自然杀伤细胞或巨噬细胞是否已被清除，或者是否注射雌二醇+孕酮以纠正细胞因子可能导致的卵巢功能降低，联合给予肿瘤坏死因子-α+γ干扰素可使80%以上的胚胎流产。这些细胞因子也会使IRF1+/+ C57BL/6雌性小鼠流产，但不会使与IRF1+/+ DBA/2交配怀孕的IRF1-/-雌性小鼠流产。CBA×DBA/2模型中的自然流产和细胞因子促进的流产均被针对细胞因子刺激的血管内皮细胞和单核细胞表达的fgl2凝血酶原酶[校正后]的抗体所阻断；在体内用抗体清除粒细胞也可预防肿瘤坏死因子-α+干扰素-γ诱导的流产。母体子宫胎盘血管中细胞因子引发的血栓形成/炎症过程会导致流产。
