Human Reproduction, Vol. 14, No. 4, 919-924,
April 1999
© 1999 European Society of Human Reproduction and Embryology
Supernatants from co-cultured endothelial cells and syncytiotrophoblast microvillous membranes activate peripheral blood leukocytes in vitro
Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
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.
Key words: activation/endothelium/leukocyte/pre-eclampsia/syncytiotrophoblast
1 To whom correspondence should be addressed at: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
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