CUTTING EDGE - CYTOKINE-DEPENDENT ABORTION IN CBA X DBA 2 MICE IS MEDIATED BY THE PROCOAGULANT FGL2 PROTHOMBINASE/

Spontaneous resorption in the CBA x DBA/2 model is attributed to NK ce lls, macrophages, and Th1-type cytokines. In vivo depletion of NK cell s by anti-asialoGM1 Ab or macrophage depletion by silicon dioxide trea tment reduced abortion rates, which could no longer be boosted by inje cting TNF-alpha (which activates NK cells) or IFN-gamma (which activat es macrophages). TNF-alpha + gamma-IFN coadministration aborted >80% o f the embryos whether or not NK cells or macrophages had been depleted or estradiol + progesterone was injected to correct potential reducti on in ovarian function by cytokines. The cytokines also aborted IRF1+/ + C57BL/6 but not IRF1-/- females pregnant by IRF1+/+ DBA/2. Both spon taneous and cytokine-boosted abortions in CBA x DBA/2 were blocked by Ab to fgl2 prothombinase expressed by cytokine-stimulated vascular end othelial cells and monocytes; in vivo Ab depletion of granulocytes als o prevented TNF-alpha + IfN-gamma-induced abortions. Cytokine-triggere d thrombotic/inflammatory processes in maternal uteroplacental blood v essels causes abortion.