Protease Chymotrypsin Mediates the Endothelial Expression of P- and E-selectin, but not ICAM and VCAM, Induced by Placental Trophoblasts from Pre-eclamptic Pregnancies

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. 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 α 2-macroglobulin (α 2M), 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-κB activity in ECs was also determined. (1) ICAM and VCAM expression was significantly increased on ECs co-cultured with both normal-TCs and PE-TCs, compared to control ECs ( P