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 3

Par2^–/– mice are protected from trophoblast oxidative injury and fetal death.

Pregnant Par2^–/– or wild-type mice were given 10 mg aPL-IgG or NH-IgG i.p. on days 8 and 12. (A) Mice were killed on day 15 of pregnancy, uteri were dissected, and FRF was calculated as described in Methods. In matings of wild-type mice, approximately 40% of the embryos of mice treated with aPL-IgG were resorbed; in contrast, Par2^–/– mice showed a reduction in aPL-IgG–induced FRF. *P < 0.05 versus NH-IgG. n = 5–7 mice per group. Data are mean ± SD. (B and C) Mice were killed on day 8, 2 h after aPL-IgG or NH-IgG injection. Uteri were dissected, and decidua sections were cut and stained with an anti-C3 antibody (B) or DHE (C) to measure superoxide generation. (B) The chromogen was DAB (brown), and the counterstain was hematoxylin. In aPL-IgG–treated wild-type mice, there was extensive C3 staining (brown) in deciduae as well as embryo debris (ED). In contrast, the decidual tissue from aPL-IgG–treated Par2^–/– mice showed minimal staining for C3 at the ectoplacental cone (ec) and intact embryo (E). (C) aPL-IgG–induced superoxide production in wild-type mice was attenuated in Par2^–/– mice. Oxidative damage in deciduae from aPL-IgG–treated PAR2 mice was minimal and not different from that in NH-IgG–treated wild-type mice. Scale bars: 100 μm (B); 40 μm (C).