JCI - Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome

Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome

Patricia Redecha, Claus-Werner Franzke, Wolfram Ruf, Nigel Mackman, Guillermina Girardi

Published in Volume 118, Issue 10

J Clin Invest. 2008; 118(10):3453–3461 doi:10.1172/JCI36089

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Figure 4

Simvastatin prevents pregnancy loss in aPL-IgG–treated mice.

(A and B) Pregnant C57BL/6 mice were given 10 mg aPL-IgG or NH-IgG i.p. on days 8 and 12, and some also received 20 μg simvastatin i.p. 18 h before administration of aPL-IgG (n = 5–11 mice per group). (A) Mice were killed on day 15 of pregnancy, uteri were dissected, and FRF was calculated. Treatment with simvastatin prevented fetal loss. ^†P < 0.01 versus aPL-IgG plus simvastatin. Data are mean ± SD. (B) Uteri from day 15 of pregnancy. There were 5 fetuses and 3 resorptions (asterisks) in the uterus of an aPL-IgG–treated mouse, while the uterus of a mouse that received aPL-IgG plus simvastatin contained 7 fetuses and no resorptions, similar to mice treated with NH-IgG (not shown). Data are representative of observations in 5–8 mice per group. (C) Mice were killed on day 8, 2 h after aPL-IgG or NH-IgG injection. Decidua sections were stained with an anti-C3 antibody as in Figure 3. In aPL-IgG–treated wild-type mice, there was extensive C3 staining (brown) in deciduae as well as embryo debris. In contrast, the decidual tissue from mice treated with aPL-IgG plus simvastatin showed minimal staining for C3 and intact embryo. (D) FACS analysis of DAF expression on trophoblast-like BeWo cells. There was no difference in DAF expression between untreated BeWo cells and BeWo cells incubated with 10 μg/ml simvastatin. Scale bars: 1 cm (B); 200 μm (C, left); 50 mm (C, right).