Enhanced Upregulation of the Fcγ Receptor IIIa (CD16a) During In Vitro Differentiation of ApoE4/4 Monocytes

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Abstract
Abstract —We recently reported a positive correlation of the pool size of lipopolysaccharide receptor (CD14) dim and Fcγ receptor IIIa (CD16a) + monocytes in peripheral blood to the apolipoprotein E4 (apoE4) phenotype and a negative correlation to high density lipoprotein (HDL) cholesterol levels ( Arterioscler Thromb Vasc Biol. 1996;16:1437–1447). In this study, the in vitro differentiation of mononuclear phagocytes derived from healthy blood donors homozygous for the E3/3 or the E4/4 phenotype was analyzed during 7 days of culture in serum-free medium supplemented with macrophage colony–stimulating factor (M-CSF). The CD16a expression, which indicates Fc receptor–dependent phagocytic activity, increased to a significantly higher level in apoE4/4 monocytes than in apoE3/3 cells. The costimulatory molecule CD40, which indicates antigen-presenting capacity, was upregulated more strongly in apoE3/3 monocytes compared with E4/4 cells, but the difference did not reach a significant level. The expression of differentiation-associated surface proteins (CD14, CD33, CD45) and adhesion molecules (CD11a, CD11b, CD11c, CD49d) was not significantly different between apoE3/3 and apoE4/4 monocytes. However, a significantly decreased intracellular apoE concentration and a reduced amount of secreted apoE were found in apoE4/4 monocytes during in vitro differentiation. No differences were found in the surface expression of the low density lipoprotein receptor–related protein (CD91) and the uptake of fluorescence labeled low density lipoprotein between apoE3/3 and apoE4/4 monocytes. These data indicate that the apoE4/4 phenotype significantly influences the M-CSF–dependent differentiation of monocytes toward a more CD16a-positive phagocytic phenotype.