Cutting edge: Cytokine-dependent abortion in CBA× DBA/2 mice is mediated by the procoagulant fgl2 prothombinase

DA Clark, G Chaouat, PC Arck… - The Journal of …, 1998 - journals.aai.org
DA Clark, G Chaouat, PC Arck, HW Mittruecker, GA Levy
The Journal of Immunology, 1998journals.aai.org
Spontaneous resorption in the CBA× 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-α (which activates NK cells) or IFN-γ (which activates
macrophages). TNF-α+ γ-IFN coadministration aborted> 80% of the embryos whether or not
NK cells or macrophages had been depleted or estradiol+ progesterone was injected to …
Abstract
Spontaneous resorption in the CBA× 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-α (which activates NK cells) or IFN-γ (which activates macrophages). TNF-α+ γ-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× DBA/2 were blocked by Ab to fgl2 prothombinase expressed by cytokine-stimulated vascular endothelial cells and monocytes; in vivo Ab depletion of granulocytes also prevented TNF-α+ IFN-γ-induced abortions. Cytokine-triggered thrombotic/inflammatory processes in maternal uteroplacental blood vessels causes abortion.
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