Systemic inflammatory stimulation by microparticles derived from hypoxic trophoblast as a model for inflammatory response in preeclampsia

Abstract

To determine whether trophoblast-derived microparticles can induce different inflammatory responses of the peripheral blood mononuclear cells depending upon the state of trophoblast when the microparticles are generated. A trophoblast-derived cell line (ATCC no. CRL-1584) was cultured under normal or hypoxic conditions. Microparticles were isolated from the cell culture supernatants (microparticles from normal trophoblast; microparticles from hypoxic trophoblast). Peripheral blood mononuclear cells were cultured alone or cocultured with either microparticles from normal trophoblast or microparticles from hypoxic trophoblast. After 48 hours, the peripheral blood mononuclear cells cocultured with microparticles from normal trophoblast released higher concentrations of interleukin-6 than peripheral blood mononuclear cells cultured alone. The peripheral blood mononuclear cells cocultured with microparticles from hypoxic trophoblast showed higher concentration of interleukin-6 and tumor necrosis factor alpha than peripheral blood mononuclear cells cocultured with microparticles from normal trophoblast, after 24 hours and 48 hours. More intense and rapid inflammatory response of peripheral blood mononuclear cells was observed with microparticles from hypoxic trophoblast than with microparticles from normal trophoblast. This difference might explain the exaggerated systemic inflammatory response as a result of placental hypoxia in preeclampsia.