O72. Monocyte–macrophage system in pregnancy complications from the prospective of extracellular vesicles

Abstract

Introduction Successful pregnancy is based on the immunological balance between the maternal immunity and the feto-placental immune system. The activity of the monocyte–macrophage (MO–Mph) system is a critical step in placental homeostasis. The bilateral effects between MO–Mph-derived extracellular vesicles (EVs) and neighboring cells or the microenvironmental EVs and MO–Mph are well-known. On the one hand, EVs released from Mph-s have both autocrine and paracrine effects including the regulation of the differentiation of local MOs into Mph-s, the induction of inflammation-induced apoptosis, or the regulation of antigen presentation. It is also well-defined that infections modify the content of Mph-derived EVs which than stimulate pro-inflammatory responses and may have a role in pregnancy complications. Objective The aim of our study was the characterization of the interactions between circulating EVs and the MO–Mph system in pregnancy complications. Methods Characterization of in vivo apoptosis and circulating MO subsets and also the effects of circulating MVs on MO function were followed up. Multicolor flow cytometry was used for the characterization of circulating microvesicles (MVs) and apoptotic bodies (ABs), and an in vitro co-culture system was designed for the identification of the effects of pregnancy associated circulating MVs. Results Significantly higher amounts of circulating ABs could be detected in pre-eclamptic plasma compared to the healthy pregnants. The binding ability of circulating MVs to human leukocytes did not differ. The distribution of MO subsets was typical for preeclampsia: higher amounts of CD14+/HLA-DR+ Mo-s and significantly lowers levels of CD14dim+ MOs could be detected. On the other hand, neither the expression level of HLA-DR on circulating MOs differed, nor the circulating MVs modified the HLA-DR expression in an in vitro culture system. Conclusion Our studies on the interactions between trophoblast derived MVs (tMVs) and infections in the development of preeclampsia suggested that tMVs induced IL-6 production in human leukocytes and the combined effect of LPS and tMVs resulted in an upregulation of the synthesis of the pro-inflammatory cytokines, IL-6 and TNFa. Our results confirm a reciprocal effect between circulating MVs and maternal MO-Mph system which may have both local and systemic consequences in the development of preeclampsia.