Cytokine-dependent abortion in CBA x DBA/2 mice is mediated by the procoagulant fgl2 prothrombinase [correction of prothombinase].
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.
Clark
D A
DA
McMaster University, Hamilton, Ontario, Canada. clarkd@fhs.csu.McMaster.ca
Chaouat
G
G
Arck
P C
PC
Mittruecker
H W
HW
Levy
G A
GA
D000022:Abortion, Spontaneous / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D003433:Crosses, Genetic; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D005260:Female; D005340:Fibrinogen; D006098:Granulocytes / Q000276:immunology; D007106:Immune Sera / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics; D011247:Pregnancy; D013925:Thromboplastin / Q000276:immunology / Q000502:physiology*
D016207:Cytokines; D004268:DNA-Binding Proteins; C490637:Fgl2 protein, mouse; D007106:Immune Sera; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D007371:Interferon-gamma; D005340:Fibrinogen; D013925:Thromboplastin