Endothelial cells and peripheral blood mononuclear cells are a potential source of extraplacental activin a in preeclampsia.

Abstract

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 TNFalpha 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 TNFalpha (P < 0.05). Human umbilical vein endothelial cells secreted activin A spontaneously and in response to TNFalpha (P < 0.05), but recombinant IL-1beta 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 TNFalpha, 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.