title: 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.
authors.affiliation: Immunology Research Centre, St. Vincent's Hospital, Melbourne, Victoria, Australia. jennifer.mcrae@svhm.org.au
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McRae
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Russell
authors.forename: Joanne Sj
authors.initials: JS
authors.lastname: Chia
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dwyer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001081:Apyrase / Q000502:physiology*; D016764:Cell Polarity; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011225:Pre-Eclampsia / Q000517:prevention & control*; D011247:Pregnancy; D013599:Systole; D018417:Th1 Cells / Q000502:physiology
chemical_list: D015703:Antigens, CD; D001081:Apyrase; C067869:CD39 antigen