Atherosclerosis and Lipoproteins |
From the Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
Correspondence to Prof Dr Gerd Schmitz, Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. E-mail gerd.schmitz{at}klinik.uni-regensburg.de
AbstractHeterogeneity
of peripheral blood monocytes is characterized by specific
patterns in the membrane expression of Fc
-receptor III
(Fc
RIII/CD16) and the lipopolysaccharide receptor (LPS
receptor CD14), allowing discrimination of distinct subpopulations. The
aim was to analyze the correlation of these phenotypic
differences to the early interaction of freshly isolated monocytes with
modified lipoproteins by the use of either enzymatically degraded low
density lipoprotein (E-LDL), acetylated low density lipoprotein
(ac-LDL), oxidized low density lipoprotein (ox-LDL), or native low
density lipoprotein. Highest E-LDL binding was observed on
CD14high CD16+
monocytes as determined by flow cytometry, suggesting a selective
interaction of E-LDL with distinct subpopulations of monocytes. E-LDL
induced rapid foam cell formation both in predifferentiated
monocyte-derived macrophages and, in contrast to ac-LDL or
ox-LDL, also in freshly isolated peripheral blood
monocytes. This was accompanied by upregulation of the 2 class B
scavenger receptors CLA-1/SR-BI (CD36 and LIMPII
Analogous-1/scavenger receptor type B class I) and CD36. Cellular
binding and uptake of E-LDL was neither competed by ac-LDL nor the
class A scavenger-receptor inhibitor polyinosinic acid but
was partially inhibited by an excess of ox-LDL. In predifferentiated
monocyte-derived macrophages, an anti-CD36 antibody inhibited
cellular binding and uptake of E-LDL by
20%, suggesting that
recognition of these hydrolase-modified low density lipoprotein
particles is mediated only in part by the class B scavenger receptor
CD36.
Key Words: scavenger receptors CD36 enzymatically degraded LDL atherogenesis
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