Trophoblast cells primed with vasoactive intestinal peptide enhance monocyte migration and apoptotic cell clearance through αvβ3 integrin portal formation in a model of maternal-placental interaction.

DANIEL PAPARINI; ESTEBAN GRASSO; GUILLERMINA CALO; DAIANA VOTA; VANESA HAUK; ROSANNA RAMHORST; CLAUDIA PEREZ LEIROS

MOLECULAR HUMAN REPRODUCTION.

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2015

1360-9947

STUDY QUESTION:Is apoptotic cell phagocytosis by monocytes modulated by pathways elicited by vasoactive intestinal peptide (VIP) action on trophoblast ?SUMMARY ANSWER:Targeting trophoblast cells with VIP induces monocyte migration, polarization to anti-inflammatory phenotypes and apoptotic trophoblast cell clearance which involves increased αvβ3 integrin expression on phagocytic cells and binding to thombospondin 1.WHAT IS KNOWN ALREADY:Monocytes recruited to the maternal-placental interface interact with trophoblast cells and differentiate to alternatively activated macrophages involved in the silent clearance of apoptotic cells. Vasoactive intestinal peptide (VIP) is an immunomodulatory polypeptide synthesized at the human placenta that can target both trophoblast cells and monocytes/macrophages. Integrin αvβ3 and thrombospondin 1 are involved in the formation of a phagocytic portal for the immunosuppressant clearance of apoptotic cells.STUDY DESIGN, SIZE, DURATION:This is a laboratory-based study studying monocytes isolated from peripheral blood of healthy women (n=33) and their interaction in vitro with first trimester trophoblast cell lines.PARTICIPANTS/MATERIALS, SETTING, METHODS:Peripheral blood monocytes were isolated from healthy volunteers by Percoll gradient and tested in co-culture settings with first trimester trophoblast cell lines (Swan 71 and HTR8) or with trophoblast cell conditioned media obtained in the presence or absence of 10 or 100 nM.VIP The effect of VIP-conditioned media on monocyte migration was assessed through transwell systems and monocyte/macrophage phenotype was determined by flow cytometry. Phagocytosis of apoptotic cells and the mechanisms involved in phagocytic portal formation were assessed by flow cytometry, confocal microscopy, immunological blockade and RT-PCR.MAIN RESULTS AND THE ROLE OF CHANCE:Exposing cells to 100 nM VIP increased the migration of monocytes towards trophoblast cell conditioned media (VIP conditioned medium) (P