1. Mononuclear Cells Negatively Regulate Endothelial Ca 2+ Signaling.
- Author
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Rengarajan A, Austin JL, Stanic AK, Patankar MS, and Boeldt DS
- Subjects
- Pregnancy, Female, Humans, Human Umbilical Vein Endothelial Cells metabolism, Monocytes metabolism, Cytokines metabolism, Adenosine Triphosphate metabolism, Leukocytes, Mononuclear metabolism, Signal Transduction
- Abstract
Endothelial Ca
2+ signaling has important roles to play in maintaining pregnancy associated vasodilation in the utero-placenta. Inflammatory cytokines, often elevated in vascular complications of pregnancy, negatively regulate ATP-stimulated endothelial Ca2+ signaling and associated nitric oxide production. However, the role of direct engagement of immune cells on endothelial Ca2+ signaling and therefore endothelial function is unclear. To model immune-endothelial interactions, herein, we evaluate the effects of peripheral blood mononuclear cells (PBMCs) in short-term interaction with human umbilical vein endothelial cells (HUVECs) on agonist-stimulated Ca2+ signaling in HUVECs. We find that mononuclear cells (10:1 and 25:1 mononuclear: HUVEC) cause decreased ATP-stimulated Ca2+ signaling; worsened by activated mononuclear cells possibly due to increased cytokine secretion. Additionally, monocytes, natural killers, and T-cells cause decrease in ATP-stimulated Ca2+ signaling using THP-1 (monocyte), NKL (natural killer cells), and Jurkat (T-cell) cell lines, respectively. PBMCs with Golgi-restricted protein transport prior to interaction with endothelial cells display rescue in Ca2+ signaling, strongly suggesting that secreted proteins from PBMCs mediate changes in HUVEC Ca2+ signaling. We propose that endothelial cells from normal pregnancy interacting with PBMCs may model preeclamptic endothelial-immune interaction and resultant endothelial dysfunction., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)- Published
- 2023
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