EXTRACELLULAR ACIDOSIS DRIVES THE DIFFERENTIATION OF HUMAN MONOCYTES INTO DENDRITIC-LIKE CELLS

ERRA DIAZ , FERNANDO; SABATTÉ , JUAN; DUETTE , GABRIEL; DANTAS , EZEQUIEL; GEFFNER , JORGE

MAR DEL PLATA

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS 2017; 2017

Differentiation of monocytes into macrophages and dendritic cells(DCs) is likely determined by the properties of the inflammatory milieu,however, little is known about the identity of the factors thatcontrol the polarization of monocytes toward each of these fates.Extracellular acidosis is a common feature of inflammation and thetumor microenvironment. Here, we analyzed the ability of extracellularacidosis to modulate monocyte?s differentiation profile. CulturingPBMCs or isolated monocytes(>85% purity) for 7 days in mediumsupplemented with 10% FCS adjusted to pH 6.5, in the presenceof PHA (2 μg/ml) or allogeneic lymphocytes (monocyte-lymphocyteratio 1:4), resulted in the appearance of an adherent spindle-shapedpopulation of cells displaying a DC-like phenotype, characterized bythe expression of CD1a, CD1c, DC-sign, HLA-DR and low/undetectableCD14. This effect was not observed in cells cultured at neutralpH. Taking the expression of CD1a as a marker of DCs, we foundthat isolated monocytes cultured with PHA for 7 days, at pH 6.5 or7.3, resulted in 70±10% vs 0.8±0.6% of CD1a+ cells respectively(mean±SE,n=6,p