Trophoblast cells prevent Neutrophil Extracellular Trap-induced damage and promote vascular transformation signals in neutrophils.

G. CALO, F. SABBIONE, N. PASCUALI, I. KEITELMAN, D. VOTA, D. PAPARINI, R. RAMHORST, F. PARBORELL, A. TREVANI AND C. PÉREZ LEIRÓS.

Buenos Aires

Congreso; International Federation of Placenta Association meeting 2019; 2019

Objectives Normal placentation entails a highly regulated interaction of maternal leukocytes and invasive trophoblast cells. Circulating neutrophils are found activated during pregnancy and even more during pathological pregnancies. Vasoactive Intestinal Peptide (VIP) is a pleiotropic peptide with immunomodulatory effects through its action on VPAC1 and VPAC2 receptors, both found in neutrophils. Our aim was to explore the effects of neutrophils and neutrophil extracellular trap formation (NETs) on trophoblast cell function and whether trophoblast cell-derived factors condition neutrophils to favor angiogenesis and promote an anti-inflammatory environment required of normal pregnancy. Methods Peripheral blood neutrophils were isolated from healthy volunteers and tested in vitro with human first trimester trophoblast cell line (Swan 71) conditioned media (CM) or with VIP. Trophoblast cell and neutrophil profiles were assessed by RT‐qPCR, flow cytometry and confocal microscopy. Trophoblast migration was evaluated using the wound healing assay and to evaluate in vivo angiogenesis the experimental model of chorioallantoic membrane of quail embryos assay was employed.Results Activated neutrophils induced a proinflammatory profile and impaired trophoblast cell migration; conditioning them with 10 nM VIP prevented this latter effect (closure%±SE Tb alone: 52.0±1.8; Tb+neutrophils 30.7±4.1; Tb+neutrophils+VIP: 42.8±4.6; P