Macrophage-derived interleukin-33 is a critical factor for placental growth

Abstract

s / Placenta 34 (2013) A1–A99 A11 including SynA and Gcm1. Similar treatment of Sirt1-null mTSC showed this effect to be Sirt1-dependent. Conclusion: Sirt1 regulates mTSC proliferation and differentiation. Lack of Sirt1 hinders mTSC differentiation. Sirt1 activation, in contrast, specifically induces the labyrinthine lineage. Further characterization of Sirt1-null mTSC and placentas may help elucidate mechanisms important for placental development and disease. http://dx.doi.org/10.1016/j.placenta.2013.06.036 NI.13. MACROPHAGE-DERIVED INTERLEUKIN-33 IS A CRITICAL FACTOR FOR PLACENTAL GROWTH Valerie Fock, Harald Zeisler, Martin Knofler, Jurgen Pollheimer Medical University of Vienna, Vienna, Austria Interleukin (IL)-33, a novel IL-1 superfamily member and ligand for the Thelper type-2-associated receptor ST2L, has been linked to several human pathologies including rheumatoid arthritis, asthma and cardiovascular disease. Recently, elevated levels of the natural IL-33 decoy receptor soluble ST2 have been reported in sera of pre-eclamptic women. Objectives: Our aim was to characterize the expression pattern of IL-33 and its receptor in the human placenta and to investigate the yet unknown role of the IL-33/ST2L pathway during healthy pregnancy. Methods: Placental and decidual specimens were obtained from elective terminations offirst trimester pregnancies. Expression and localization of IL33 and ST2L were analyzed by flow cytometry, Western blot and immunofluorescence stainings. IL-33 levels in culture supernatants of macrophages were determined by ELISA. Bromodeoxyuridine incorporation assays and ki67 stainingswere performed to assess proliferation inprimary trophoblast model systems. The phosphorylation status of proliferation-associated kinases was evaluated by Western blot and immunofluorescence stainings. Results: In this studywe show that CD45+CD14+macrophages represent the major source of cytoplasmic IL-33 in the uteroplacental unit. Furthermore, the presence of IL-33 was confirmed in culture supernatants of primary villous and decidual macrophages. Membranous expression of ST2L was detected on different trophoblast subtypes, identifying them as potential target cells for secreted IL-33. Indeed, recombinanthuman IL-33 significantly increased proliferation of primary trophoblasts as well as of villous cytotrophoblasts (CTBs) and cell column trophoblasts (CCTs) in placental explant cultures. These effects were fully abolished upon addition of soluble ST2. IL33-dependent AKT and ERK1/2 activation was observed in primary trophoblasts, villous CTBs and CCTs. In agreement with this observation, chemical inhibitors against PI3K (LY294002) andMEK1/2 (UO126) efficiently blocked IL-33-induced trophoblast proliferation in all model systems used. Conclusion: With IL-33 we define for the first time a macrophage-derived regulator of placental growth during early pregnancy. This studywas funded by the Austrian National Bank (grant 13955) and the Austrian Science Fund (P-22687-B13, P-25187-B13). http://dx.doi.org/10.1016/j.placenta.2013.06.037 P1.1. DECIDUAL ACUTE ATHEROSISUPDATING AND TESTING DIAGNOSTIC CRITERIA Patji Alnaes-Katjavivi , Fiona Lyall , Borghild Roald , Christopher Redman , Annetine Staff 1 Women and Children's Division, Oslo University Hospital (OUS), Oslo, Norway; 2 Institute of Medical Genetics, University of Glasgow, Glasgow, UK; Nuffield Department of ObstetricsG Department of Pathology, Oslo University Hospital (OUS), Oslo, Norway Background: Acute atherosis (AA) of the uteroplacental spiral arteries is an understudied lesion, associatedwith infarction of the placental parenchyma and preeclampsia, both contributing to deleterious pregnancy outcome. The lesion resembles early stage atherosclerosis, and we hypothesize that it has a spectrum of expression and may also identify a subset of women at elevated risk for atherosclerotic arterial disease later in life. AA is not specific to pregnancies affected by preeclampsia, but can affect uncomplicated, normotensive pregnancies. Acute atherosis, originally described by Hertig (1945), is defined by presence of subendothelial lipidfilled foam cells, fibrinoid necrosis and perivascular leukocyte infiltration (Hanssens M et al. Eur J Obstet Gynecol 1998). Previous definitions lack quantitative criteria and are subject to observer bias. The aim of the study was to update the diagnostic criteria of decidual acute atherosis, and to develop methods of quantification of lesions. Methods: We have developed revised criteria to diagnose and quantify decidual uterospiral acute atherosis. We evaluate serial sections of formalin fixated and paraffin embedded decidual basalis tissue samples, collected by vacuum suction from 250 caesarean deliveries. Results: Our revised definition expands on the traditional CD68+ marker for the macrophage-type of foam cells, recording residual smooth muscle (desmin antibody), fibrinoid (PAS), quantity and localization of trophoblast (cytokeratin antibody), and perivascular mononuclear cells. The findings for each patient yield a stratified diagnosis of decidual acute atherosis, depending on the sum of characteristics present for the visualized decidual arteries. Reliability of diagnosis for acute atherosis, using these predefined criteria, will be presented as Kappa values between the first three abstract authors. Conclusions:We present a new, quantitativemethod for defining decidual acute atherosis. Quantification may prove useful when exploring the association between acute atherosis and pregnancy phenotype, and whether presence of lesion relates to excessive risk of future atherosclerotic CVD. http://dx.doi.org/10.1016/j.placenta.2013.06.038 P1.2. ABNORMAL PERICYTE RECRUITMENT IN FETAL PLACENTAL VASCULATURE: CAUSE OF IUGR AND FETAL THROMBOTIC VASCULOPATHY IN ADAMS-OLIVER SYNDROME?