Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium

Abstract

This study was prompted by the observation that decidual endothelial cells (DECs), unlike endothelial cells (ECs) of blood vessels in normal skin, kidney glomeruli and brain, express surface-bound C1q in physiologic pregnancy. This finding was unexpected, because deposits of C1q are usually observed in pathologic conditions and are associated with complement activation. In the case of DECs, we failed to detect immunoglobulins and C4 co-localized with C1q on the cell surface. Surprisingly, DECs expressed mRNA for the three chains of C1q and secreted detectable level of this component in serum-free medium. The ability to synthesize C1q is acquired by DECs during pregnancy and is not shared by ECs obtained from endometrium and from other sources. Cell-associated C1q has a molecular weight similar to that of secreted C1q and is released from DECs following treatment with heparinase or incubation at low pH. This suggests that C1q binds to DECs and it is not constitutively expressed on the cell surface. C1q is localized at contact sites between endovascular trophoblast and DECs and acts as an intercellular molecular bridge because adhesion of endovascular trophoblast to DECs was inhibited by antibodies to C1q and to a receptor recognizing its globular portion expressed on trophoblast.

C1q as a unique player in angiogenesis with therapeutic implication in wound healing

“…However, the involvement of circulating C1q, although potentially possible, is unlikely because binding of plasma C1q to target cells usually leads to complement activation through the classical pathway, which apparently does not occur in wound healing, as suggested by the lack of C4 and C3 deposition and the in vivo findings with the C3-deficient mice. An alternative possibility supported by the in situ hybridization data is that C1q is produced by ECs and interacts with specific receptors and other binding sites on the cell surface, as already shown for decidual ECs (22).…”

“…Our previous findings that C1q is deposited on the ECs of vessels in maternal decidua but is absent in other vascular districts (22) raised the question of whether C1q may be associated with newly formed vessels. To this end, we examined the presence and distribution of C1q in wound healing, a tissue characterized by active angiogenesis.…”

“…2 B-E). We have investigated specifically the C1qC mRNA expression because we have previously shown that ECs isolated from normal skin express only the mRNA for A and B chains of C1q (22).…”

“…This analysis was prompted by our previous finding that C1q is deposited on ECs of decidua, serving the important function of promoting adhesion of endovascular trophoblasts and their migration through the interendothelial cell junctions of spiral arteries to partially replace ECs (22). Because decidua is a newly formed tissue at an embryo implantation site, we hypothesized that cell-bound C1q may also play a role in promoting angiogenesis in other situations.…”

Role of Complement Component C1q in the Onset of Preeclampsia in Mice

“…C1q is widely distributed in human decidual stroma and is actively synthesized by migrating extravillous trophoblasts. 8,9 In addition, we demonstrated previously that C1q deficiency was associated with impaired labyrinth development and decidual vessel remodeling and increased fetal death in mice. 9 These results suggest that defective local production of C1q may be involved in PE.…”