Wang Y, Adair C D, Coe L, Weeks J W, Lewis D F, Alexander J S
Department of Obstetrics and Gynecology, Louisiana State University Medical Center, Shreveport, USA.
J Soc Gynecol Investig. 1998 Sep-Oct;5(5):237-43. doi: 10.1016/s1071-5576(98)00023-9.
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.
内皮细胞激活增加被认为在子痫前期的病理生理学中起重要作用。我们的目的是研究子痫前期中性粒细胞与内皮细胞的黏附是否增加，以及内皮细胞表面黏附分子的表达是否上调。
从正常（n = 10）和子痫前期（n = 9）的人脐静脉（HUVECs）中分离内皮细胞。从正常、健康的未孕女性志愿者中分离中性粒细胞。将新鲜分离的中性粒细胞用51Cr标记，然后将标记的中性粒细胞与汇合的正常和子痫前期内皮单层细胞共同孵育。然后进行黏附试验。为了确定子痫前期内皮细胞表面黏附分子是否导致中性粒细胞与内皮细胞黏附增加，通过酶联结合试验检测P-选择素、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和E-选择素的细胞黏附分子表达。此外，还对用抗P-选择素、抗ICAM-1、抗VCAM-1和抗E-选择素抗体预处理的HUVECs进行了黏附试验。
与正常妊娠的HUVECs相比，子痫前期妊娠的中性粒细胞与HUVECs的黏附显著增加（P < .01）。子痫前期分离的HUVECs中，P-选择素的细胞表面黏附分子表达显著更高（P < .01），ICAM-1显著更低（P < .05），而正常和子痫前期妊娠的HUVECs中VCAM-1和E-选择素表达没有差异。与未处理的细胞相比，用抗P-选择素、抗ICAM-1、抗VCAM-1和抗E-选择素预处理的正常HUVECs上的中性粒细胞与内皮细胞黏附没有差异。然而，与未处理的细胞相比，用抗P-选择素、抗ICAM-1、抗VCAM-1和抗E-选择素预处理子痫前期HUVECs可完全或部分阻断中性粒细胞与内皮细胞的黏附。
与正常对照组相比，子痫前期妊娠分离的HUVECs中中性粒细胞黏附显著增加。这种增加似乎是细胞表面黏附分子P-选择素上调的结果。P-选择素表达升高可能在中性粒细胞与内皮细胞的高黏附性中起重要作用，并导致与子痫前期相关的血管并发症。
