VIP enhances trophoblast cell-mediated monocyte migration, phagocytosis and M2 phenotype expression

2. DANIEL PAPARINI, ESTEBAN GRASSO, GUILLERMINA CALO, DAIANA VOTA, ROSANNA RAMHORST, CLAUDIA PÉREZ LEIRÓS

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

The generation and maintenance of the maternal-placental interface is a dynamic process that involves the concerted action of different population of leucocytes and mediators to favor a tolerogenic micro-environment. Monocytes (Mo) are recruited to the maternal-placental interface and ?educated? by trophoblast cells (Tb) to express an M2 alternative activation profile, thus  contributing to the maintenance of immune  homeostasis. On the basis that vasoactive intestinal peptide (VIP) has anti-inflammatory and immunosuppressive effects, we evaluated the functional profile of Mo co-cultured with Tb and their modulation by VIP. We used an in vitro model of co-culture of first trimester trophoblast cell line (Swan-71) and Mo isolated from PBMCs (Percoll gradient) from healthy volunteers. The expression of cytokines and VIP receptors (VPAC) was evaluated in Mo by FACS and RT-PCR. Mo treated with VIP increased the % of  CD39 while diminished IL-12 and TNF-a positive cells. When Mo were co-cultured with Tb in the presence of 10 nM VIP the % of IL-10 positive cells was enhanced (X±ES= 29,5±3,5; 32,4±4,3 vs 16,3±4,3; P<0,05) as well as CD39 (X±ES= 35,6±14,4; 42,4±14,0 vs 6,6±2,3; P<0,05) without changes in IL-12 and TNF-a. Moreover, when Mo were cultured with conditioned media (CM) obtained from Tb pre-treated with VIP (10nM) for 20 h, we observed an increased in IL-10 and reduced in TNF-a positive cells were observed. These CM also enhanced phagocytosis of apoptotic Tb cells (% of CD14/CFSE cells: CM-VIP 22,0% vs. control media 13,5%; P<0,05) and apoptotic neutrophils (71,5% vs control: 41,1%; P<0,05) and Mo migration. These results support that VIP acting on Tb and promoting Mo functional profile modulation would favor immune homeostasis maintenance in the maternal placental-interface.