Cutting Edge: Cytokine-Dependent Abortion in CBA × DBA/2 Mice Is Mediated by the Procoagulant fgl2 Prothombinase

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.