title: Enhanced upregulation of the Fc gamma receptor IIIa (CD16a) during in vitro differentiation of ApoE4/4 monocytes.
abstract: We recently reported a positive correlation of the pool size of lipopolysaccharide receptor (CD14)dim and Fc gamma 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.
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Stöhr
authors.forename: G
authors.initials: G
authors.lastname: Schindler
authors.forename: G
authors.initials: G
authors.lastname: Rothe
authors.forename: G
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D000328:Adult; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000032:analysis* / Q000378:metabolism; D018845:CD11 Antigens / Q000097:blood; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood; D008055:Lipids / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D009000:Monocytes / Q000145:classification / Q000166:cytology* / Q000276:immunology; D010586:Phagocytes / Q000276:immunology; D017452:Receptors, IgG / Q000097:blood*; D011971:Receptors, Immunologic / Q000097:blood; D018110:Receptors, Lipoprotein / Q000097:blood; D015854:Up-Regulation
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D018845:CD11 Antigens; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; C072413:apolipoprotein B receptor; D017493:Leukocyte Common Antigens