Protease chymotrypsin mediates the endothelial expression of P- and E-selectin, but not ICAM and VCAM, induced by placental trophoblasts from pre-eclamptic pregnancies
Protease chymotrypsin mediates the endothelial expression of P- and E-selectin, but not ICAM and VCAM, induced by placental trophoblasts from pre-eclamptic pregnancies
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DOI：
10.1016/s0143-4004(03)00132-2
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发表时间：
2003-09-01
期刊：
影响因子：
3.8
通讯作者：
Alexander, JS
中科院分区：
文献类型：
--
作者：
Wang, Y;Zhang, Y;Alexander, JS
目的：可溶性内皮细胞黏附分子(ICAM、VCAM和PECAM)是血管内皮细胞活化的标志物，在妊娠期间母体循环中升高，在妊娠合并子痫前期(PE)时甚至进一步升高。为了确定妊娠期间内皮细胞激活剂的可能来源，我们研究了胎盘滋养层细胞(TCS)释放的因子是否激活内皮细胞(ECs)以增强ECs上黏附分子的表达。我们还观察了胎盘细胞释放的蛋白水解酶是否能诱导内皮细胞表面分子的表达。方法：将融合的内皮细胞与正常(n=9)、胎盘(n=8)的胎盘TC或来自PE胎盘培养的胎盘条件培养液(CM，n=7)共同培养。采用双抗体夹心法测定ICAM、VCAM、P-选择素和E-选择素的含量。在共培养体系中检测蛋白水解酶抑制物α(2)-巨球蛋白(α(2)M)、凝血酶抑制物(TI)和胰凝乳蛋白酶抑制物(CI)。用核糖核酸酶保护试验(RPA)检测ICAM、VCAM、P-选择素和E-选择素的mRNAs。结果：(1)与正常TCS和PE-TCS共同培养的ECs，ICAM和VCAM的表达均显著高于对照组(P
Objectives: Soluble endothelial-cell adhesion molecules (ICAM, VCAM and PECAM) are markers of endothelial activation, and are elevated in the maternal circulation during pregnancy and even further increased in pregnancies complicated by pre-eclampsia (PE). To identify possible sources of endothelial activators during pregnancy, we addressed whether factors released from placental trophoblast cells (TCs) activate endothelial cells (ECs) to enhance adhesion molecule expression on ECs. We also examined whether proteases released by placental cells induce the endothelial cell surface molecule expression in PE.Methods: Confluent ECs were co-cultured with placental TCs derived from normal (n=9) or PE (n=8) pregnancies or with placental conditioned media (CM) derived from PE placental cultures (n=7). ICAM, VCAM, P-selectin and E-selectin were quantified using an enzyme-linked immunosorbent assay (ELISA). The protease inhibitors alpha(2)-macroglobulin (alpha(2)M), thrombin inhibitor (TI) and chymotrypsin inhibitor (CI) were tested in the co-culture system. mRNAs for ICAM, VCAM, P-selectin and E-selectin were determined by RNase protection assay (RPA). NF-kappaB activity in ECs was also determined.Results: (1) ICAM and VCAM expression was significantly increased on ECs co-cultured with both normal-TCs and PE-TCs, compared to control ECs (P