Overexpression of CD39 protects in a mouse model of preeclampsia

CD39 (NTPDase1), a critical immune and vascular ecto-nucleotidase, hydrolyses pro-inflammatory and pro-thrombotic nucleotides (adenosine-5-triphosphate (ATP) and adenosine diphosphate) to adenosine. In humans, CD39 is the dominant ecto-nucleotidase in placental trophoblastic tissues and modulates ATP-dependent trophoblastic functions. CD39 is an integral component of regulatory T cells (Treg), which are central to immunological tolerance and maintenance of normal pregnancy. We examined the impact of CD39 overexpression in a mouse model of preeclampsia. Matings were performed between virginal BALB/c female (wild-type (WT) or CD39 transgenic (CD39TG)) and C57BL/6 male mice. On days 10 and 12 of pregnancy BALB/c Th1-polarized cells were injected. Systolic blood pressure (SBP) was measured throughout pregnancy. Mice were sacrificed at day 15 of pregnancy. Following transfer of Th1-polarized cells, SBP of pregnant WT mice increased (118 +/- 3mmHg to 142 +/- 5mmHg). Although ultrastructural changes were evident in the kidney this was not accompanied by significant proteinuria. SBP remained unchanged (115 +/- 2mmHg to 114 +/- 3mmHg) in pregnant CD39TG mice without evidence of renal lesions. We conclude that gestational hypertension can be induced in mice following transfer of maternally derived Th1-polarized cells and that overexpression of CD39 is protective in this model.