Activation of endothelial cells in preeclampsia: increased neutrophil-endothelial adhesion correlates with up-regulation of adhesion molecule P-selectin in human umbilical vein endothelial cells isolated from preeclampsia.

Abstract

Increased endothelial activation has been suggested to be important in the pathophysiology for preeclampsia. Our objective was to examine whether in preeclampsia neutrophil adherence to endothelial cells is increased and whether endothelial cell-surface adhesion molecule expression is up-regulated. Endothelial cells were isolated from normal (n = 10) and preeclamptic (n = 9) human umbilical veins (HUVECs). Neutrophils were isolated from normal, healthy, nonpregnant female volunteers. Freshly isolated neutrophils were labeled with 51Cr, and labeled neutrophils were coincubated with confluent normal and preeclamptic endothelial monolayers. Adhesion assays were then performed. To determine whether in preeclampsia endothelial cellular-surface adhesion molecules are responsible for increased neutrophil-endothelial adhesion, cellular adhesion molecule expression of P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin were examined by an enzyme-linked binding assay. Furthermore, adhesion assays were also performed on HUVECs pretreated with antibodies against P-selectin, ICAM-1, VCAM-1, and E-selectin. Neutrophil adhesion to the HUVECs from preeclamptic pregnancies was significantly increased compared with neutrophil adhesion to the HUVECs from normal pregnancies (P < .01). Expression of cellular-surface adhesion molecule of P-selectin was significantly higher (P < .01) and ICAM-1 was significantly lower (P < .05) in HUVECs isolated from preeclampsia than from normal controls, whereas there was no difference for VCAM-1 and E-selectin expression between HUVECs from normal and preeclamptic pregnancies. No differences were found for neutrophil-endothelial adhesion on normal HUVECs pretreated with anti-P-selectin, anti-ICAM-1, anti-VCAM-1, and anti-E-selectin compared with the untreated cells. However, pretreatment of preeclampsia HUVECs with anti-P-selectin, anti-ICAM-1, anti-VCAM-1, and anti-E-selectin completely or partially blocked the neutrophil-endothelial adhesion compared to the untreated cells. There is a significant increase in neutrophil adhesion to HUVECs that are isolated from preeclamptic pregnancies compared with normal controls. This increase appears to be a result of up-regulation of the cell-surface adhesion molecule P-selectin. Elevated P-selectin expression may play a significant role in neutrophil-endothelial hyperadhesiveness and contribute to vascular complications associated with preeclampsia.