title: Vitamin C enhances phagocytosis of necrotic trophoblasts by endothelial cells and protects the phagocytosing endothelial cells from activation.
abstract: Preeclampsia is a pregnancy-specific disease characterised by maternal hypertension that is preceded by endothelial cell activation and an inappropriate inflammatory response. The exact cause of preeclampsia is unclear but this disease is known to be induced by a placental factor and it is hypothesised that oxidative stress may also contribute to its pathogenesis. We have shown that dead trophoblasts shed from the placenta can be phagocytosed by endothelial cells and that phagocytosis of necrotic, but not apoptotic, trophoblasts leads to endothelial cells activation. Since phagocytosis may be accompanied by an oxidative burst which may lead to damage/activation of the phagocyte, in this study we have investigated whether the antioxidant vitamin C can protect endothelial cells that phagocytose necrotic trophoblasts from activation. We demonstrate that treatment of phagocytosing endothelial cells with vitamin C induced an increase in the phagocytosis of necrotic trophoblasts but that activation of the phagocytosing endothelial cells was prevented. Treatment of phagocytosing endothelial cells with vitamin C also prevented the increase in IL-6 secretion that normally accompanies phagocytosis of necrotic trophoblasts. Thus treatment of endothelial cells with vitamin C appears to modify both the phagocytosis of necrotic trophoblasts and the response of the endothelial cells to the necrotic trophoblastic material.
authors.affiliation: Department of Obstetrics & Gynaecology, Faculty of Medical & Health Sciences, The University of Auckland, Auckland, New Zealand. q.chen@auckland.ac.nz
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Jones
authors.forename: P
authors.initials: P
authors.lastname: Stone
authors.forename: L-M
authors.initials: LM
authors.lastname: Ching
authors.forename: L
authors.initials: L
authors.lastname: Chamley
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D009336:Necrosis; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D011225:Pre-Eclampsia / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000473:pathology; D014471:Umbilical Veins / Q000166:cytology; D055815:Young Adult
chemical_list: D000975:Antioxidants; C508600:IL6 protein, human; D015850:Interleukin-6; D001205:Ascorbic Acid