© 1999 American Heart Association, Inc.
Rapid Communication |
Expression of Human Scavenger Receptor Class B Type I in Cultured Human Monocyte-Derived Macrophages and Atherosclerotic Lesions
Presented in part at the 71st Scientific Sessions of the American Heart Association, Dallas, Tex, November 8–11, 1998.
From the Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Correspondence to Ken-ichi Hirano, MD, PhD, Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail khirano{at}kb3.so-net.ne.jp
Abstract—The scavenger receptor
class B type I (SR-BI) and its human homologue CLA-1 (CD36
and LIMPII Analogous-1) have
recently been identified to bind HDL and mediate the selective uptake
of HDL lipids. Tissue distribution of both murine and human receptors
is quite similar, in that they are expressed abundantly in liver and
steroidogenic tissues. However, expression and function of the human
SR-BI (hSR-BI), in the periphery of reverse cholesterol
transport such as macrophages, are still unclear. In the
present study, we have raised two different kinds of anti–hSR-BI
polypeptide antibodies (Abs): one against the extracellular domain and
the other against the intracellular domain. We have investigated
the expression of hSR-BI mRNA and immunoreactive mass in freshly
isolated cultured human monocyte-derived macrophages (hM
)
and in atherosclerotic lesions. Contrary to the earlier report, hSR-BI
mRNA was expressed in cultured hM and markedly upregulated with
differentiation, determined by Northern blot and reverse
transcriptase–based polymerase chain reaction analyses. The
mRNA expression pattern during differentiation of hM was very
similar to those of SR class A and another member of SR class B, CD36.
Protein expression was confirmed by Western blot analyses with
the above Abs to show a major 83-kDa band. Modified lipoproteins such
as oxidized LDL and acetylated LDL induced a 5-fold increase in
mRNA and protein expression of hSR-BI. Confocal
immunofluorescence microscopy demonstrated that
hSR-BI immunoreactive mass was detectable as a
heterogeneous, punctate staining pattern. Furthermore,
immunohistochemical analysis showed that immunoreactive mass of
hSR-BI was detected in foam cells in human aortic atherosclerotic
lesions and that there was no significant difference of staining
patterns between the two Abs. This study clearly demonstrates that
hSR-BI is expressed in the lipid-laden macrophages in human
atherosclerotic lesions, suggesting that it is very important to know
its function and regulation in hM to understand the biological
utility of this molecule.
Key Words: atherosclerosis • human scavenger receptor class B type I • high-density lipoprotein • reverse cholesterol transport • scavenger receptor
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