Phagocytosis of apoptotic trophoblast cells by human endometrial endothelial cells induces proinflammatory cytokine production.
OBJECTIVE
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.


METHODS
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.


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.


CONCLUSIONS
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.
Peng
Bing
B
Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, New Haven, CT 06520, USA.
Koga
Kaori
K
Cardenas
Ingrid
I
Aldo
Paulomi
P
Mor
Gil
G
D017209:Apoptosis; D002478:Cells, Cultured; D004717:Endometrium / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010587:Phagocytosis; D014327:Trophoblasts / Q000166:cytology*
D018836:Inflammation Mediators; D015850:Interleukin-6