Figure 6
Figure 6. TF expression by myeloid cells but not fetal-derived cells contributes to aPL-induced fetal loss. (A) Low TF female mice (mTF−/−,hTF+) mated with wild-type males (mTF+/+) and wild-type female mice mated with wild-type males (mTF+/+ × mTF+/+) were treated on days 8 and 12 with aPL-IgG or NH-IgG. On day 15, fetal resorption rates were calculated as described 19in “Materials and methods, Murine aPL-induced fetal loss model.” Approximately 40% of the embryos in wild-type matings treated with aPL-IgG were resorbed. Low TF female mice mated with wild-type males showed a reduction in aPL-induced fetal resorption frequency compared with wild-type mice (P < .005). Error bars here and in panel B are SD. (B) Pregnant TFfloxed/floxed and TFfloxed/floxed/LysM-Cre mice were treated with aPL-IgG or NH-IgG on days 8 and 12 of pregnancy. Fetal resorption frequency was calculated as described19 in “Materials and methods, Murine aPL-induced fetal loss model.” Treatment with aPL-IgG caused an increase in fetal resorptions in TFfloxed/floxed mice (*P < .001 versus NH-IgG). TFfloxed/floxed/LysM-Cre mice were protected from fetal loss induced by aPL-IgG. Fetal resorption frequency in these mice was comparable with TFfloxed/floxed mice treated with NH-IgG. (C) Immunohistochemical analysis for neutrophils in sections of deciduas from aPL-IgG–treated mice. Intense staining for neutrophils (brown color) was observed in deciduas from TFfloxed/floxed mice treated with aPL-IgG (Ci). In contrast, less neutrophil infiltration was observed in deciduas from TFfloxed/floxed/LysMCre mice that had received aPL-IgG (Cii). Counterstain: hematoxylin. Original magnification × 500. (D) Superoxide (O2−) generation in decidual tissue was determined using dihydroethidium fluorescence. aPL-induced O2− formation (Di) is attenuated in TFfloxed/floxed/LysM-Cre mice (Dii) and low TF mice (Diii) to a similar extent to NH-IgG–treated mice (Div). Original magnification × 800.

TF expression by myeloid cells but not fetal-derived cells contributes to aPL-induced fetal loss. (A) Low TF female mice (mTF−/−,hTF+) mated with wild-type males (mTF+/+) and wild-type female mice mated with wild-type males (mTF+/+ × mTF+/+) were treated on days 8 and 12 with aPL-IgG or NH-IgG. On day 15, fetal resorption rates were calculated as described 19in “Materials and methods, Murine aPL-induced fetal loss model.” Approximately 40% of the embryos in wild-type matings treated with aPL-IgG were resorbed. Low TF female mice mated with wild-type males showed a reduction in aPL-induced fetal resorption frequency compared with wild-type mice (P < .005). Error bars here and in panel B are SD. (B) Pregnant TFfloxed/floxed and TFfloxed/floxed/LysM-Cre mice were treated with aPL-IgG or NH-IgG on days 8 and 12 of pregnancy. Fetal resorption frequency was calculated as described19  in “Materials and methods, Murine aPL-induced fetal loss model.” Treatment with aPL-IgG caused an increase in fetal resorptions in TFfloxed/floxed mice (*P < .001 versus NH-IgG). TFfloxed/floxed/LysM-Cre mice were protected from fetal loss induced by aPL-IgG. Fetal resorption frequency in these mice was comparable with TFfloxed/floxed mice treated with NH-IgG. (C) Immunohistochemical analysis for neutrophils in sections of deciduas from aPL-IgG–treated mice. Intense staining for neutrophils (brown color) was observed in deciduas from TFfloxed/floxed mice treated with aPL-IgG (Ci). In contrast, less neutrophil infiltration was observed in deciduas from TFfloxed/floxed/LysMCre mice that had received aPL-IgG (Cii). Counterstain: hematoxylin. Original magnification × 500. (D) Superoxide (O2) generation in decidual tissue was determined using dihydroethidium fluorescence. aPL-induced O2 formation (Di) is attenuated in TFfloxed/floxed/LysM-Cre mice (Dii) and low TF mice (Diii) to a similar extent to NH-IgG–treated mice (Div). Original magnification × 800.

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