title: Trophoblast debris extruded from preeclamptic placentae activates endothelial cells: a mechanism by which the placenta communicates with the maternal endothelium.
abstract: BACKGROUND
  Preeclampsia is characterized by maternal endothelial dysfunction. While the mechanisms leading to preeclampsia are unclear, a factor(s) from the placenta is responsible for triggering the disease. One placental factor implicated in triggering preeclampsia is trophoblast debris which may transmit pathogenic signals from the placenta to endothelial cells. In this study, we investigated whether trophoblast debris from preeclamptic placentae triggered endothelial cell activation.
  
  
  METHODS
  Trophoblast debris from preeclamptic or normotensive placentae, or trophoblast debris from normal placental explants that had been cultured with preeclamptic (n = 14) or normotensive sera (n = 14) was exposed to endothelial cells. Activation of the endothelial cells was quantified by cell surface ICAM-1 and U937 adhesion to endothelial cells. The levels of IL-1β, pro-caspase-1 and active caspase-1 in the trophoblast debris were measured.
  
  
  RESULTS
  Compared to controls, the levels of ICAM-1 and U937 adhesion to endothelial cells were significantly increased following exposure of the endothelial cells to trophoblast debris from preeclamptic placentae or placentae treated with preeclamptic sera. The levels IL-1β, pro-caspase-1 and active caspase-1 were significantly increased in both trophoblast debris from preeclamptic placentae and placentae treated with preeclamptic sera.
  
  
  CONCLUSIONS
  These results provide the first direct evidence that trophoblast debris produced from preeclamptic placentae or placentae treated with preeclamptic sera can activate the endothelium.
  
  
  CONCLUSIONS
  Trophoblast debris from preeclamptic but not normotensive placentae can induce endothelial cell activation. This may be one mechanism by which the preeclamptic placenta communicates with the maternal endothelium to induce activation of the endothelium.
authors.affiliation: The Hospital of Obstetrics & Gynaecology, Fudan University, China; Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand.
authors.forename: F
authors.initials: F
authors.lastname: Shen
authors.affiliation: Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.affiliation: Maternal Fetal Medicine, Auckland City Hospital, New Zealand.
authors.forename: S
authors.initials: S
authors.lastname: Snowise
authors.affiliation: Maternal Fetal Medicine, Auckland City Hospital, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: DeSousa
authors.affiliation: Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand; Maternal Fetal Medicine, Auckland City Hospital, New Zealand; Gravida The National Centre for Growth and Development, The University of Auckland, New Zealand.
authors.forename: P
authors.initials: P
authors.lastname: Stone
authors.affiliation: Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand.
authors.forename: C
authors.initials: C
authors.lastname: Viall
authors.affiliation: The Hospital of Obstetrics & Gynaecology, Fudan University, China; Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand. Electronic address: q.chen@auckland.ac.nz.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand; Gravida The National Centre for Growth and Development, The University of Auckland, New Zealand.
authors.forename: L
authors.initials: L
authors.lastname: Chamley
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D018799:Intercellular Adhesion Molecule-1; D020170:Caspase 1
keywords: Caspase-1; Endothelium; IL-1β; Preeclampsia; Syncytial nuclear aggregates; Trophoblast debris