Overexpression of CD39 protects in a mouse model of preeclampsia

Abstract

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 ± 3 mmHg to 142 ± 5 mmHg). Although ultrastructural changes were evident in the kidney this was not accompanied by significant proteinuria. SBP remained unchanged (115 ± 2 mmHg to 114 ± 3 mmHg) 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.

Splenocyte transfer exacerbates salt‐sensitive hypertension in rats

“…Researchers studying hypertensive disease progression have used different approaches to transfer these cells, including negative selection of T cells using magnetic bead sorting (Barhoumi et al, 2011;Chen et al, 2018b;Guzik et al, 2007;Hoch et al, 2009;Iulita et al, 2019;Ji et al, 2014;Kinsey et al, 2009;Kvakan et al, 2009;Marvar et al, 2010;Mian, Barhoumi, Briet, Paradis, & Schiffrin, 2016;Pons et al, 2013;Senchenkova, Russell, Kurmaeva, Ostanin, & Granger, 2011;Trott et al, 2014;Wu et al, 2014Wu et al, , 2016, positive selection for T-regulatory cells (Barhoumi et al, 2011;Cornelius et al, 2015;Kasal et al, 2012;Mian et al, 2016;Turner et al, 2010) or flow-assisted cell (FAC) sorting (Chen et al, 2018b;Kassan, Galan, Partyka, Trebak, & Matrougui, 2011;Kvakan et al, 2009;Yang et al, 2008). In addition, cell culture techniques have been used to enrich specific T-cell subsets before transfer (Chen et al, 2018b;Hayakawa et al, 2000;McRae, Russell, Chia, & Dwyer, 2013;Meyers, Tomaszewski, Glass, & Chen, 1998;Wallace et al, 2012;Wang et al, 2006). Important work has demonstrated that the sex of the donor and of the recipient can influence the hypertensive phenotype of the recipient, which has revealed an integral role of sex hormones in the development of hypertension (Ji et al, 2014;Pollow et al, 2014).…”

Danger Signals From ATP and Adenosine in Pregnancy and Preeclampsia

“…In addition, CD73 knockout mice, which are likely to have elevated ATP levels, display preeclampsia-like symptoms, such as proteinuria, inflammation, endothelial dysfunction, and glomerular endotheliosis, [87][88][89] whereas CD39 overexpression inhibited the induction of preeclampsia in mice. 90 …”

The Impact of Purinergic System Enzymes on Noncommunicable, Neurological, and Degenerative Diseases

“…Following transfer of Th1-polarized cells, SBP of E-NTPDase 1 transgenic mice remained unchanged, without evidence of renal lesions, while an increase was observed in pregnant wild-type mice. Thus, the authors have concluded that E-NTPDase 1 overexpression can be protective in a mouse model of preeclampsia [ 100 ].…”