Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, New Haven, CT 06520, USA.
Am J Reprod Immunol. 2010 Jul 1;64(1):12-9. doi: 10.1111/j.1600-0897.2010.00815.x. Epub 2010 Mar 4.
Apoptosis is a normal constituent of trophoblast turnover in the placenta; however in some cases, this process is related to pregnancy complications such as preeclampsia. Recognition and engulfment of these apoptotic trophoblast cells is important for clearance of dying cells. The aim of this study was to show the cross talk between human endometrial endothelial cells (HEECs) and apoptotic trophoblast cells in an in vitro coculture model and its effect on cytokine production by HEECs.
Fluorescent-labeled HEECs were cocultured with fluorescent-labeled apoptotic human trophoblast cells. Confocal microscopy and flow cytometry were used to show the interaction between these two types of cells. Cytokine profiles were determined using multiplex analysis.
HEECs are capable to phagocytose apoptotic trophoblasts. This activity is inhibited by the phagocytosis inhibitor cytochalasin B. Phagocytosis of apoptotic trophoblast cells induced the secretion of the proinflammatory cytokines interleukin-6 and monocyte chemoattractant protein-1 by HEECs.
This study provides the first evidence that HEECs have an ability to phagocytose apoptotic trophoblasts. Furthermore, we demonstrated an inflammatory response of HEECs after phagocytosing the apoptotic trophoblast cells. This event may contribute to the inflammatory response in both normal pregnancy and pathologic pregnancy such as preeclampsia.
细胞凋亡是胎盘滋养层细胞更替的一个正常组成部分；然而，在某些情况下，这个过程与子痫前期等妊娠并发症有关。识别和吞噬这些凋亡的滋养层细胞对于清除死亡细胞很重要。本研究旨在展示体外共培养模型中人类子宫内膜内皮细胞 (HEEC) 与凋亡的滋养层细胞之间的相互作用及其对 HEEC 细胞因子产生的影响。
用荧光标记的 HEEC 与荧光标记的凋亡人滋养层细胞共培养。共聚焦显微镜和流式细胞术用于显示这两种细胞之间的相互作用。使用多重分析确定细胞因子谱。
HEEC 能够吞噬凋亡的滋养层细胞。吞噬作用抑制剂细胞松弛素 B 抑制了这种活性。凋亡滋养层细胞的吞噬作用诱导 HEEC 分泌促炎细胞因子白细胞介素 6 和单核细胞趋化蛋白 1。
本研究首次提供证据表明 HEEC 具有吞噬凋亡滋养层细胞的能力。此外，我们证明了吞噬凋亡滋养层细胞后 HEEC 的炎症反应。这种事件可能导致正常妊娠和子痫前期等病理妊娠中的炎症反应。
