Supernatants from co-cultured endothelial cells and syncytiotrophoblast microvillous membranes activate peripheral blood leukocytes in vitro.
There is evidence for both endothelial cell and peripheral blood leukocyte (PBL) activation in pre-eclampsia. Syncytiotrophoblast microvillous membranes (STBM) are shed in greater quantities from the placenta in pre-eclampsia, disrupt cultured endothelial cells in vitro and may be the immediate cause of the maternal syndrome. The aim of this study was to determine if endothelial cells co-cultured with STBM release factors that can activate PBL in vitro. Flow cytometry was used to measure changes in intracellular free ionized calcium ([Ca2+]i), pH (pHi) and reactive oxygen species (iROS) as indices of leukocyte activation. PBL from male non-pregnant donors was exposed to supernatants from human umbilical vein endothelial cells (HUVEC) cultured with STBM. The time course of changes in [Ca2+]i, pHi and iROS was determined and compared with appropriate control measurements. The test supernatants caused significant activation of granulocytes and monocytes in terms of increases in [Ca2+]i and falls in pHi and release of iROS. Lymphocytes responded only with respect to increases in iROS. The results define a possible mechanism for the activation of PBL in pre-eclampsia, as being secondary to endothelial cell activation caused by circulating STBM shed in excess amounts from the placenta.
von Dadelszen
P
P
Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford, UK.
Hurst
G
G
Redman
C W
CW
D002118:Calcium / Q000378:metabolism; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D011225:Pre-Eclampsia / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*
D017077:Culture Media, Conditioned; D017382:Reactive Oxygen Species; D002118:Calcium