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CUTTING EDGE |
*
McMaster University, Hamilton, Ontario, Canada;
INSERM Unite 131, Hôpital Antoine Béclère, Clamart, France;
Amgen Institute, Princess Margaret Hospital, University of Toronto, and
Multiorgan Transplant Group, The Toronto Hospital, University of Toronto, Toronto, Canada
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-
(which activates NK cells) or
IFN-
(which activates macrophages). TNF- + -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 prothombinase expressed by cytokine-stimulated vascular
endothelial cells and monocytes; in vivo Ab depletion of granulocytes
also prevented TNF- + IFN--induced abortions. Cytokine-triggered
thrombotic/inflammatory processes in maternal uteroplacental blood
vessels causes abortion.
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