Adhesion molecules of syncytiotrophoblast microvillous membranes inhibit proliferation of human umbilical vein endothelial cells

It has been shown previously that syncytiotrophoblast microvillous membrane s (STBM), isolated from normal or pre-eclampsia placentae, specifically inh ibit the proliferation of cultured human umbilical vein endothelial cells ( HUVEC) and disrupt the cell monolayer without causing cell death. We have p reviously shown that this anti-proliferative activity resides in a self-agg regating complex in which eight proteins, namely integrins alpha(5) (CD49e) and alpha(v) (CD51), dipeptidyl peptidase IV (DPP IV, CD26), alpha-actinin , transferrin receptor (TfR, CD71), transferrin, placental alkaline phospha tase (PLAP) and monoamine oxidase A (MAO-A) were identified. In the present study, we investigated which of these components causes the anti-prolifera tive activity of STEM. Antibodies against integrin alpha(5) and alpha(v) an d DPP IV all reduced the STBM-induced inhibition of proliferation of HUVEC, which was also reversed by added fibronectin. A preparation of FLAP inhibi ted endothelial proliferation, but this was not due to enzymatic activity. The preparation was shown to be impure with more than 12 bands present on C oomassie blue stained SDS-PAGE gels. These included integrins alpha(5) and alpha(v), which could account, at least in part, for the inhibitory activit y. We could not exclude, however, the possibility of other unidentified fac tors being involved. We conclude that adhesion molecules account for a majo r part of the anti-proliferative activity of STBM; these appear to compete for ligands in the extracellular matrix or serum with the appropriate recep tors on HUVEC. (C) 2000 Harcourt Publishers Ltd.