VIP promotes apoptotic cell phagocytosis by monocytes/macrophages through αvß3 integrin-thrombospondin portal formation and enhanced trophoblast migration in a model of maternal-placental interaction.

D. PAPARINI, E.. GRASSO, D.VOTA, V. HAUK, G. CALO, R. RAMHORST, C. PÉREZ LEIRÓS

Buenos Aires

Congreso; LASID-FAIC-FAIC Meeting,; 2015

Sociedad Argentina de Inmunología

Background. Homeostasis maintenance at the early maternal-fetal interface requires active tissue remodelling processes and the clearance of apoptotic cells by macrophages in an immunosuppressant microenvironment. Vasoactive intestinal peptide (VIP) is a pleiotropic polypeptide synthesized by trophoblast cells that induces an anti-inflammatory profile in monocytes and macrophages (Mo/Ma). Here we explored VIP effect on trophoblast-monocyte interaction with special focus on Mo phagocytosis of apoptotic cells and trophoblast cell wound healing. Methods. Mo were purified by Percoll from PBMC of healthy volunteers and cultured in the presence/absence of VIP (1-100nM) or with conditioned media (CM) from first trimester human cytotrophoblast cell line (Swan-71) (Tb) treated or not with VIP (CM-VIP). Apoptosis was induced in Tb with camptothecin. CFSE-labelled apoptotic cell phagocytosis by CD14+ cells and αvß3 expression was assessed by flow cytometry and confocal microscopy. Thrombospondin1 expression was determined by RT-qPCR. Wound healing assays were run in trophoblast monolayers.Results. CM from Tb cells enhanced phagocytosis of apoptotic cells and induced αvß3 integrin re-localization and expression on Mo/Ma vs. DMEM (frecuency % X±SE: 77.1±2.0 vs. 49.6±1.5; P