© 1998 American Heart Association, Inc.
Original Contributions |
Enhanced Upregulation of the Fc
Receptor IIIa (CD16a) During In Vitro Differentiation of ApoE4/4 Monocytes
From the Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
Correspondence to Gerd Schmitz, MD, Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauß-Allee 11, D-93053 Regensburg, Germany. E-mail gerd.schmitz{at}klinik.uni-regensburg.de
Abstract—We recently reported a
positive correlation of the pool size of lipopolysaccharide
receptor (CD14)dim and Fc 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.
Key Words: monocytes • apolipoprotein E • CD16a • CD40 • low density lipoprotein receptor–related protein
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