Abstract P132: Differential and Sex Dependent Expression of Vasopressin Receptors by B Cells, NK Cells, and Dendritic Cells

Hypertension(2019)

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摘要
Arginine vasopressin (AVP) has been shown to play a role in preeclampsia, a hypertensive and immune-mediated disorder in pregnancy. Chronic infusion of AVP during gestation into wild-type mice results in the pregnancy-specific physiological changes (hypertension, kidney damage, fetal growth restriction) as well as increased CD4+ T H 1 and T H 17 associated cytokine responses observed in human pregnancies affected by preeclampsia. Further, human CD4+ T cells isolated from preeclamptic women were found to differentially express AVP receptors (AVPRs) 1a and 2 compared to control pregnancies. Abnormalities in other immune cells are seen during preeclampsia, including auto-antibody production (B cells), poor placental development (natural killer (NK) cells), and increased pro-inflammatory T cells responses (via dendritic cells (DC)). We, therefore, hypothesize that B cells, NK cells, and DC express AVPRs. To begin to understand 1) the expression pattern of AVPRs on CD4- lymphocytes and 2) if there are differences in expression between males and females, we evaluated the expression of AVPR 1a, 2, and 1b specifically on B cells, NK cells, and DC. Each subset was purified via negative selection from de-identified human peripheral blood mononuclear cells obtained through Leukocyte Reduction System (LRS) cone donors at the DeGowin Blood Center followed by qPCR for AVPR 1a, 2, and 1b expression (N=6 per cell type). B cells, NK cells, and DC expressed all three AVPRs 1a, 2, and 1b. All three lymphocyte populations showed a lower expression of AVPR1b compared to expression of 1a and 2, with B cells having the lowest expression of AVPR1b (p<0.05). Interestingly, while B cells and NK cells showed no differences in expression based on sex of the donor, DC isolated from male donors more highly expressed AVPR1b compared to female donors (p=0.0035). In conclusion, we demonstrate that B cells, NK cells, and DC highly express AVPR1a and 2, and that DC expression of AVPRs is sex dependent. Further investigation into the utilization of these receptors by these immune cells and the potential impact of sex-specific differences may elucidate newly identified mechanisms of AVP and immune interactions in not only preeclampsia, but possibly other cardiovascular-related diseases as well.
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