MBL interferes with endovascular trophoblast invasion in pre-eclampsia

Abstract

The spiral arteries undergo physiologic changes during pregnancy, and the failure of this process may lead to a spectrum of pregnancy disorders, including pre-eclampsia. Our recent data indicate that decidual endothelial cells (DECs), covering the inner side of the spiral arteries, acquire the ability to synthesize C1q, which acts as a link between endovascular trophoblast and DECs favouring the process of vascular remodelling. In this study, we have shown that sera obtained from pre-eclamptic patients strongly inhibit the interaction between extravillous trophoblast (EVT) and DECs, preventing endovascular invasion of trophoblast cells. We further demonstrated that mannose-binding lectin (MBL), one of the factor increased in pre-eclamptic patient sera, strongly inhibits the interaction of EVT with C1q interfering with the process of EVT adhesion to and migration through DECs. These data suggest that the increased level of MBL in pre-eclampsia may contribute to the failure of the endovascular invasion of trophoblast cells.

Figure 1

Immunofluorescence analysis of cells isolated from first trimester placenta. Purified EVTs were stained with mAb antihuman cytokeratin 7 (a) and DECs (b) with monoclonal anti-VE-cadherin. Images were acquired with Leica DM3000 microscope. Original magnification 100x.

Figure 2

Effect of serum from pre-eclamptic and normal pregnant women in EVT/DEC interaction. Analysis of the effect of sera obtained from PE or normal women on the adhesion of EVTs to DECs (a), to C1q (c) and on transendothelial migration through DECs (b). EVTs were preincubated with PE or control sera (1 : 50). The results are expressed as percent of adhesion in reference to a standard curve. For each group, the line in the middle of the box represents the median. The lower and the upper edges of the box are the 1st and 3rd quartile, respectively.

Figure 3

Analysis of serum levels of MBL in pre-eclamptic and control women. The level of oligomerized MBL in sera was measured using an MBL oligomer ELISA kit. The results are expressed as box plot graphs, in which the line in the middle of the box represents the median; the lower and the upper edges of the box are the 1st and 3rd quartile, respectively.

Figure 4

Analysis of MBL effect in the interaction between EVTs to DECs. To investigate the effect of MBL in the interaction between EVTs and DECs we performed adhesion (a) and migration assays through DECs, (b) in the presence of 2 μg/mL of MBL. The graph in (c) confirm the ability of EVT to adhere to C1q, while MBL was not able to promote adhesion of EVT as compared to BSA used as negative control. The ability of MBL to inhibit the adhesion process was also evaluated on the binding of EVT to C1q (C1q + MBL). **P < 0.01; ***P < 0.001; ^§ P < 0.00001.