Biology subjects

Wadsack, C.

Publications and source records attributed to Wadsack, C..

3 recordsLinked to original sources

bioRxiv2023

Myeloperoxidase enhances the migration of human choriocarcinoma JEG-3 cells

Myeloperoxidase (MPO) is one of the most abundant proteins in neutrophil granules. It catalyzes the production of reactive oxygen species, which are important in inflammation and immune defense. MPO also binds to several proteins, lipids, and DNA to alter their function. MPO is present at the feto-maternal interface during pregnancy, where neutrophils are abundant. In this study, we determined the effect of MPO on JEG-3 human choriocarcinoma cells as a model of extravillous trophoblasts (EVTs) during early pregnancy. We found that MPO was internalized by JEG-3 cells and localized to the cytoplasm and nuclei. MPO internalization and activity enhanced JEG-3 cell migration, whereas this effect was impaired by pre-treating cells with heparin, to block cellular uptake, and MPO-activity inhibitor 4-ABAH. This study identifies a novel mechanism for the effect of MPO on EVT function during normal pregnancy and suggests a potential role of MPO in abnormal pregnancies. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/526039v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@5fd67borg.highwire.dtl.DTLVardef@1fa4f7dorg.highwire.dtl.DTLVardef@78a0c3org.highwire.dtl.DTLVardef@1828760_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Gestational diabetes mellitus dysregulates the PD-1/PD-L1 axis at the feto-maternal interface

The most common pregnancy complication is gestational diabetes mellitus (GDM), which is a glucose tolerance disorder. Obesity and older maternal age, which are associated with low-grade systemic inflammation, are the main risk factors for GDM. To evaluate the complexity and differences in the immune landscape at the fetal-maternal interface, we examined the maternally derived tissue, decidua basalis (DB), from healthy women, women with obesity, and women with GDM using flow cytometry, western blot, and gene expression analysis. Our results showed that the immune cell composition of DB is not altered by obesity; however, in GDM pregnancies, the DB displays a dysregulated PD-1/PD-L1 axis and significantly reduced regulatory T cell (Treg) infiltration, suggesting reduced local immunosuppression. Our study provides a detailed picture of the immune landscape at the fetal-maternal interface in normal, obese, and GDM pregnancies. This will aid our understanding of possible dysfunctional immune mechanisms in GDM.

immunology↗

bioRxiv2021

Differential serotonin uptake mechanisms at the human maternal-fetal interface

Mechanisms regulating serotonin (5-HT) homeostasis at the maternal-fetal interface are important for proper placental functioning and fetal (neuro)development. Here we studied 5-HT uptake mechanisms in human primary trophoblasts, feto-placental endothelial cells and cord blood platelets, all isolated directly after birth. Trophoblasts and cord blood platelets demonstrated high-affinity 5-HT uptake with similar Michaelis constant (Km) values (0.60{+/-}0.27 and 0.65{+/-}0.18 M, respectively). In contrast, feto-placental endothelial cells displayed saturation kinetics only over the low-affinity range of 5-HT concentrations (Km=782{+/-}218 M). 5-HT uptake into trophoblasts was inhibited by various psychotropic drugs targeting high-affinity serotonin transporter (SERT), and into feto-placental endothelial cells by an inhibitor of low-affinity transporters. SERT mRNAs were abundant in trophoblasts, but sparse in feto-placental endothelial cells; the opposite was found for transcripts of the low-affinity plasma membrane monoamine transporter (PMAT). These results show for the first time the presence of functional 5-HT uptake systems in feto-placental endothelial cells and fetal platelets, cells in direct contact with the fetal blood plasma. Data also emphasize sensitivity of 5-HT transport into trophoblasts, cells facing maternal blood, to various psychotropic drugs. The multiple, high- and low-affinity, systems present for cellular 5-HT uptake highlight the importance of maintaining 5-HT homeostasis at the maternal-fetal interface.

cell biology↗