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Endothelial Cells and Peripheral Blood Mononuclear Cells Are a Potential Source of Extraplacental Activin A in Preeclampsia

Nuffield Department of Obstetrics and Gynaecology (D.S.T., C.W.G.R., I.L.S.), University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; Department of Obstetrics and Gynaecology (S.M.), Royal Free University College London Medical School, London WC1E 6HX, United Kingdom; and School of Biological and Molecular Sciences (N.P.G.), Oxford Brookes University, Headington, Oxford OX3 0BP, United Kingdom

Address all correspondence and requests for reprints to: Dr. Dionne Tannetta, Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington OX3 9DU, United Kingdom. E-mail: d.s.tannetta{at}obs-gyn.ox.ac.uk.

An excessive systemic inflammatory response, involving endothelial cells and leukocytes, underlies the maternal symptoms of preeclampsia. Activin A is raised in preeclampsia, suggesting a possible involvement in its pathophysiology. The placenta is the main source of activin A in normal pregnancy. We investigated whether peripheral blood mononuclear cells (PBMCs) and endothelium, activated by proinflammatory stimuli, were a potential source of activin A in preeclampsia. Both endotoxin and TNF stimulated activin A secretion by PBMCs from nonpregnant, preeclamptic, and matched normal pregnant women (P < 0.05). Pregnancy increased the responsiveness of PBMCs to endotoxin (P < 0.05), whereas only the preeclamptic group were significantly more responsive to TNF (P < 0.05). Human umbilical vein endothelial cells secreted activin A spontaneously and in response to TNF (P < 0.05), but recombinant IL-1ß and IL-6 had no significant effect over the 72-h culture period. Inhibin A and follistatin were undetectable (<2 pg/ml and < 20 pg/ml, respectively) in PBMCs and human umbilical vein endothelial cell culture media. These data suggest that PBMCs and endothelium, activated by TNF, could be extraplacental sources of activin A in preeclampsia. The pathological significance of increased activin A in preeclampsia is unknown, although it may have a role in the mechanisms underlying endothelium dysfunction.

This work was supported by Tommy’s, The Baby Charity, Grant 54.

Abbreviations: CM, Culture medium; FCS, fetal calf serum; HUVEC, human umbilical vein endothelial cell; MP, matched normal pregnant; NP, nonpregnant; PBMC, peripheral blood mononuclear cell; PE, preeclampsia.

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