TROPHOBLAST CELLS PREVENT NEUTROPHIL EXTRACELLULAR TRAPINDUCED DAMAGE AND PROMOTE VASCULAR TRANSFORMATION SIGNALS IN NEUTROPHILS

CALO, GUILLERMINA; SABBIONE, FLORENCIA; PASCUALI, NATALIA; KEITELMAN, IRENE; VOTA, DAIANA M.; PAPARINI, DANIEL E.; RAMHORST, ROSANNA; PARBORELL, FERNANDA; TREVANI, ANALIA; PÉREZ LEIRÓS, CLAUDIA

Congreso; IFPA; 2019

SLIMP-IFPA

Objectives: Normal placentation entails a highly regulated interaction of maternal leukocytes and invasive trophoblast cells. Circulating neutrophils are activated during pregnancy and even more during pathological pregnancies. Vasoactive Intestinal Peptide (VIP) has immunomodulatory effects through its action on VPAC1 and VPAC2 receptors, both expressed by neutrophils. Our aim was to explore the effects of neutrophils and neutrophil extracellular traps (NET) on trophoblast cell function and whether trophoblast cell-derived factors and VIP condition neutrophils to favor angiogenesis and promote an anti-inflammatory environment required for normal pregnancy.Methods: Peripheral blood neutrophils were isolated from healthy volunteers and cultured with human first trimester trophoblast cell line (Swan 71) conditioned media (CM) or with VIP. NET formation was induced with monosodium urate crystals (MSU). Trophoblast cell and neutrophil profiles were assessed by RT-qPCR, flow cytometry and confocal microscopy. Trophoblast migration was evaluated by wound healing assays and angiogenesis with the chorioallantoic membrane of quail embryos model assay.Results: NETs isolated from MSU-activated neutrophils hindered trophoblast cell migration (%±SE Tb: 92.5±1.4; Tb+NETs: 70.0±3.3; P