Phagocytosis of Necrotic but Not Apoptotic Trophoblasts Induces Endothelial Cell Activation
- 1 January 2006
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 47 (1), 116-121
- https://doi.org/10.1161/01.hyp.0000196731.56062.7c
Abstract
It is hypothesized that preeclampsia is caused by factors from the placenta that induce endothelial cell activation. Trophoblasts are cells that may be shed from the placenta, then deported in the maternal blood, and finally become trapped in the pulmonary capillaries. The ultimate fate of deported trophoblasts is unknown, but to prevent clogging of the pulmonary circulation they must be cleared from the capillary beds. We examined the hypothesis that endothelial cells phagocytose deported trophoblasts and also examined the consequent effects of the trophoblasts on endothelial cells. Fluorescently labeled trophoblast–derived choriocarcinoma cells were induced to become apoptotic or necrotic and exposed to endothelial cell monolayers. Confocal microscopy demonstrated uptake of both apoptotic and necrotic trophoblasts, and this phagocytosis could be inhibited by cytochalasin B. Phagocytosis of necrotic but not apoptotic trophoblasts induced increased endothelial intercellular adhesion molecule 1 (ICAM-1) expression, as well as increased adhesion of monocytes to endothelial cell monolayers. Inhibiting the phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase pathways blocked both expression of ICAM-1 and phagocytosis, whereas inhibition of the P42/44 mitogen-activated protein kinase pathway blocked only ICAM-1 expression. This work suggests that endothelial cells can phagocytose deported trophoblasts and that the mechanism of trophoblast death (apoptotic or necrotic) could have major effects on the maternal vascular response to shed trophoblasts.Keywords
This publication has 24 references indexed in Scilit:
- Apoptosis in the Trophoblast—Role of Apoptosis in Placental MorphogenesisJournal of the Society for Gynecologic Investigation, 2004
- Involvement of p42/p44 MAPK, JNK, and NF‐κB in IL‐1β‐induced ICAM‐1 expression in human pulmonary epithelial cellsJournal of Cellular Physiology, 2004
- Does endothelial cell activation occur with intrauterine growth restriction?BJOG: An International Journal of Obstetrics and Gynaecology, 2002
- Roles of PI3Ks in leukocyte chemotaxis and phagocytosisCurrent Opinion in Cell Biology, 2002
- Bacterial Lipopolysaccharide and Tumor Necrosis Factor Alpha Synergistically Increase Expression of Human Endothelial Adhesion Molecules through Activation of NF-κB and p38 Mitogen-Activated Protein Kinase Signaling PathwaysInfection and Immunity, 2001
- Hypertension in pregnancyJournal of Human Hypertension, 2000
- Trophoblast Deportation in Human Pregnancy—its Relevance for Pre-eclampsiaPlacenta, 1999
- Endothelial Dysfunction in PreeclampsiaSeminars in Reproductive Medicine, 1998
- An investigation of methods for enriching trophoblast from maternal bloodPrenatal Diagnosis, 1995
- TROPHOBLAST CELLS IN PERIPHERAL BLOOD FROM PREGNANT WOMENThe Lancet, 1984