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Phagocytosis of Apoptotic Trophoblast Cells by Human Endometrial Endothelial Cells Induces Proinflammatory Cytokine Production
Authors:Bing Peng  Kaori Koga  Ingrid Cardenas  Paulomi Aldo  Gil Mor
Affiliation:1. Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, New Haven, CT, USA;2. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China;3. The two authors contributed equally to this work.;4. Department of Obstetrics and Gynecology, University of Tokyo School of Medicine, Tokyo, Japan
Abstract:
Citation Peng B, Koga K, Cardenas I, Aldo P, Mor G. Phagocytosis of apoptotic trophoblast cells by human endometrial endothelial cells induces proinflammatory cytokine production. Am J Reprod Immunol 2010; 64: 12–19 Problem 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. Method of study Fluorescent‐labeled HEECs were cocultured with fluorescent‐labeled apoptotic human trophoblast cells. Confocal microscopy and flowcytometry were used to show the interaction between these two types of cells. Cytokine profiles were determined using multiplex analysis. Results 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. Conclusion 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.
Keywords:Endometrium  interleukin‐6  inflammation  monocyte chemoattractant protein‐1  preeclampsia  pregnancy
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