208. Exposing necrotic trophoblasts to endothelial cells in vitro causes increased adhesion of monocytes

Abstract

A number of studies suggest that there is a generalized endothelial cell activation and inflammatory response in preeclampsia, which may be caused by factors released from the placenta including deported trophoblasts. Trophoblasts are the placental cells that are bathed in maternal blood during pregnancy and as they become aged or damaged trophoblasts are shed from the placenta and deported into the maternal circulation. The fate of deported trophoblasts is unknown but we have found that endothelial cells can phagocytose dead trophoblasts. The aim of this study was to examine the effects of phagocytosing dead trophoblasts on endothelial cell–monocyte interactions. Methods: The trophoblast-derived cell lines Jar and Jeg-3 were induced to undergo necrotic death by freeze/thawing or apoptotic death by exposure to UV light. HMEC-1 endothelial cells were labeled with green fluorescent cell tracker stain and then exposed to necrotic or apoptotic trophoblasts for 3 or 24 h. U937 (monocyte) cells were labeled with red fluorescent stain and incubated with the HMEC-1 monolayers for 3 or 24 h. The adhesion of the U937 cells to the HMEC-1 monolayers was quantified by flow cytometry and compared to the adhesion of U937 cells to untreated HMEC-1 monolayers. Results: Exposing the HMEC-1 cells to necrotic, but not apoptotic, trophoblasts induced an approximately two-fold increase in the adhesion of U937 cells to the HMEC-1 monolayers (P = 0.01). The findings were consistent regardless of whether the HEMC-1 cells were exposed to the dead trophoblasts for 3 or 24 h. Conclusions: We have previously shown that endothelial cells phagocytose both apoptotic and necrotic trophoblasts. The results of the current study suggest that shedding necrotic trophoblasts from the placenta could induce endothelial cells to become activated resulting in increased leucocyte adhesion. Thus, dead trophoblasts may be one of the factors released from the placenta that induce preeclampsia.