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 FROMPREECLAMPSIA

OBJECTIVE: Increased endothelial activation has been suggested to be i mportant in the pathophysiology for preeclampsia. Our objective tvas t o examine whether in preeclampsia neutrophil adherence to endothelial cells is increased and whether endothelial cell-surface adhesion molec ule expression is up-regulated. METHODS: Endothelial cells were isolat ed 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 Cr- 51, and labeled neutrophils were coincubated with confluent normal and preeclamptic endothelial monolayers. Adhesion assays were then perfor med. To determine whether in preeclampsia endothelial cellular-surface adhesion molecules are responsible for increased neutrophil-endotheli al adhesion, cellular adhesion molecule expression of P-selectin, inte rcellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion mol ecule-1 (VCAM-1), and E-selectin were examined by an enzyme-linked bin ding assay. Furthermore, adhesion assays were also performed oil HUVEC s pretreated with antibodies against P-selectin, ICAM-1, VCAM-1, and E -selectin. RESULTS: Neutrophil adhesion to the HUVECs from preeclampti c pregnancies was significantly increased compared with neutrophil adh esion to the HUVECs from normal pregnancies (P <.01). Expression of ce llular-surface adhesion molecule of P-selectin was significantly highe r (P <.01) and ICAM-1 was significantly lower (P <.05) in HUVECs isola ted from preeclampsia than from normal controls, whereas there was no difference for VCAM-1 and E-selectin expression between HUVECs from no rmal and preeclamptic pregnancies. No differences were found for neutr ophil-endothelial adhesion on normal HUVECs pretreated with anti-P-sel ectin, anti-ICAM-1, anti-VCAM-1, and anti-E-selectin compared with the untreated cells. However, pretreatment of preeclampsia HUVECs with an ti-P-selectin, anti-ICAM-1, anti-CAM-1, and anti-E-selectin completely or partially blocked the neutrophil-endothelial adhesion compared to the untreated cells. CONCLUSION: There is a significant increase in ne utrophil adhesion to HUVECs that are isolated from preeclamptic pregna ncies compared with normal controls. This increase appears to be a res ult of up-regulation of the cell-surface adhesion molecule P-selectin. Elevated P-selectin expression may play a significant role in neutrop hil-endothelial endothelial hyperadhesiveness and contribute to vascul ar complications associated with preeclampsia. Copyright (C) 1998 by t he Society for Gynecologic Investigation.