© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Identification of a 
-Interferon–Responsive Element in the Promoter of the Human Macrophage Scavenger Receptor A Gene
From the Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Montreal, Quebec, Canada. Thomas Grewal is currently at the Universität Hamburg, Universitätskrankenhaus Eppendorf, Medizinische Klinik, Hamburg, Germany.
Correspondence to Dr Lise Bernier, Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal, Quebec H2W 1R7, Canada. E-mail berniel{at}ircm.qc.ca
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Abstract |
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Abstract—In the present study, we demonstrate
-interferon
(-IFN)–inducible scavenger receptor A (SR-A) mRNA expression during
the early stages of THP-1 and blood monocyte differentiation.
Predominant induction of SR-A type II mRNA parallels the increased
accumulation of cholesteryl esters under these conditions. A potential
signal transducer and activator of transcription (STAT1)
binding site (-interferon activation site) in the SR-A promoter
demonstrates -IFN–inducible DNA binding activity and is most likely
responsible for the -IFN–dependent expression of an SR-A
promoter–luciferase fusion construct. In contrast, -IFN inhibits
SR-A expression in mature macrophages as well as after
prolonged -IFN incubation of THP-1 monocytes. Taken together, these
results demonstrate opposite effects of -IFN on SR-A expression and
activity during the early versus late stages of monocyte maturation.
-IFN–induced STAT1 activation, leading to increased SR-A
expression, could therefore play an important role in the initial steps
of foam cell formation and xanthomatosis.
Key Words: scavenger receptor type A • -interferon • STAT1
• GAS element • macrophage activation
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Monocyte-derived macrophages are implicated in the development of foam cells of atherosclerotic lesions.1 The human macrophage scavenger receptor A (SR-A) binds and internalizes modified LDL, which ultimately results in the accumulation of cholesterol esters in macrophages.2 These results, together with the elevated plasma cholesterol levels and the reduced size of atherosclerotic lesions seen in SR-A/apolipoprotein E (apoE) double-knockout mice,3 have led to the hypothesis that SR-A plays an important role in the formation of foam cells during the early stages of atherosclerosis.
In humans, SR-A expression is almost entirely
restricted to macrophages, and it increases during monocyte
maturation.4 The 2 SR-A mRNA
isoforms result from alternative splicing of the same transcript from a
single gene,5 but the
functional significance of the 2 isoforms remains
unknown.6 Previous studies
have demonstrated that during early monocyte differentiation, SR-A
expression is stimulated by macrophage colony-stimulating
factor.7 This transcriptional
activation of the SR-A gene is thought to be mediated by members of the
activator protein (AP)-1 and
ets family of transcription
factors.8 9 In
contrast, -interferon (-IFN), transforming growth factor-ß1,
and tumor necrosis factor- have been shown to inhibit SR-A
expression in mature
macrophages.10 11 12 13
Recent findings have demonstrated that -IFN can inhibit
transcription of the macrophage SR-A gene by antagonizing the
AP-1 and ets transcription
factors as a result of competition between
AP-1/ets and a signal
transducer and activator of transcription (STAT1) for
limiting amounts of the transcriptional cofactors CREB-binding
protein and
p300.11
We have recently reported that SR-A–overexpressing
monocytes from a normolipidemic patient with xanthomatosis demonstrated
elevated STAT1 and -IFN–inducible protein-10 (IP-10)
expression.14 Similar
results were obtained from a number of subjects with familial
hypercholesterolemia, who frequently develop
xanthomatosis.14 We now
report that -IFN regulates SR-A expression in a
differentiation-dependent manner in THP-1 and blood-derived monocytes.
In agreement with previous reports, -IFN exhibits an
inhibitory effect on SR-A mRNA expression in mature
macrophages.10 11
In contrast, -IFN stimulates SR-A expression at early stages of
monocyte differentiation. Gel retardation and transfection experiments
suggest that -IFN–inducible STAT1 binding to a potential STAT1
element (-interferon activation site [GAS]) at position -133 to
-125 (SR-Ap) in the SR-A promoter is in part responsible for the
induction of SR-A expression and activity in -IFN–activated
monocytes. Our results explain previously discordant findings on the
role of -IFN in SR-A regulation and provide the first demonstration
that a GAS in the SR-A promoter has a regulatory function on SR-A
activity.
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Methods |
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Cell Culture
Human THP-1 monocytes were grown in RPMI 1640 medium containing 10% heat-inactivated fetal calf serum. To promote differentiation, monocytes were incubated with phorbol 12-myristate-13-acetate (PMA 0.1 µg/mL, Sigma). Human recombinant
-IFN (Gibco-BRL) was added to PMA-induced THP-1 cells at
a concentration of 25 ng/mL of medium (175 U/mL). Blood-derived
monocytes were isolated from healthy normolipidemic laboratory
personnel (ages 30 to 59; 7 men and 5 women) as
described.15 This research
was approved by the Institutional Ethics Committee, and informed
consent was obtained from all subjects.
RNA Extraction and Northern Blot
Analysis
Total RNA was isolated from 5 to
8x106 THP-1 cells with Trizol reagent
(Gibco-BRL) and analyzed by Northern blotting as
described.14 Hybridization
was performed with random-primed 2000-bp
HindIII-XbaI
human SR-A type II (nucleotides -46 to
+198216 ) or 490-bp
glyceraldehyde 3-phosphate dehydrogenase
(nucleotides 3724 to
422414 ) DNA
probes.
RT-PCR Analysis
Total RNA was reverse-transcribed (RT) with
murine Moloney leukemia virus reverse transcriptase (Gibco-BRL)
as
described.14 15
Simultaneous amplification of a 290-bp SR-A cDNA fragment
and a 376-bp glyceraldehyde 3-phosphate dehydrogenase
cDNA fragment was performed in duplicate by using primers labeled with
Hex fluorescence (University of Calgary Core DNA Services,
Calgary, Alberta, Canada) as
described.15 Determination
of STAT1 and IP-10 transcript levels was performed by
semiquantitative polymerase chain reaction (PCR) analysis and
has been described in
detail14 (also see
http://www.atvb.ahajournals.org).
Gel Mobility Shift Assays
Preparation of nuclear extracts has been previously
described in detail.14
Oligonucleotides comprising potential GAS elements from
-133 to -125 (SR-Ap:
5'-TTAGATTTTGCAAAACGTC-3'),
-813 to -805 (SR-Ad:
5'-CTCCTGGGTTCAAGCAATTC-3'),
and the AP-1 binding site from -67 to -50
(5'-AATGTGTCATTTCCTTTC-3') of
the human SR-A
gene8 9 were used
to identify the binding of transcription factors. GAS elements from the
human GTP-binding protein and IP-10 promoter
regions14 served as STAT1
binding controls. One to 2 microliters of nuclear extract (4 µg
protein) and [-32P]dATP-labeled
(Amersham, 800 Ci/mmol) double-stranded
oligonucleotides (0.5 ng,
2x105 counts per minute) were incubated for
30 minutes, and protein-DNA complexes were electrophoresed on 6%
polyacrylamide gels. A 100-fold excess of unlabeled
double-stranded human GTP-binding protein and IP-10 GAS elements or a
synthetic AP-1 oligonucleotide
(5'-GATCCGATGAGTCAGCCA-3')14
was added in some experiments.
Transfection of THP-1 Cells
Human SR-A promoter fragments from positions -290
to +54 (344 bp, pSRA-290) and from -116 to +54 (170 bp, pSRA-116)
were cloned into pGL3-Basic (Promega). Cells
(4x107) were cotransfected with 32 µg of
pSRA-290 or pSRA-116 together with 1 µg of ß-galactosidase reporter
plasmid as an internal control by using the diethylaminoethyl-dextran
method (Stratagene). Forty-eight hours after transfection,
107 cells/mL were plated and incubated for
24 to 72 hours at 37°C under various conditions. Luciferase activity
was assayed with the Promega luciferase assay system with a Berthold LB
953 luminometer and normalized to the ß-galactosidase
standard.
Lipid Loading of Cells
Preparation and acetylation (Ac) of LDL
were performed and confirmed by agarose gel electrophoresis as
described.14 15
Ac-LDL (50 µg/mL) was added to PMA-activated THP-1 cells
(with or without -IFN) in RPMI 1640 containing 10%
lipoprotein-deficient serum. Cells were incubated for 24 hours at
37°C, washed with phosphate-buffered saline, and collected for lipid
extraction.17 Lipids were
analyzed by capillary gas
chromatography18
(for details of lipid analysis, see
http://www.atvb.ahajournals.org).
Accumulation of
1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyane
(DiI) Ac-LDL (L-3484, Molecular Probes) was analyzed by
fluorescence-activated cell sorting flow cytometry
(FACScan, Becton-Dickinson) at 555 nm as
described.15
PMA-activated THP-1 cells (106) were
incubated in 10% lipoprotein-deficient serum with or without -IFN
for 24 hours, followed by incubation with 10 µg/mL DiI–Ac-LDL for 1
hour at 37°C. Cells were washed 3 times with ice-cold
phosphate-buffered saline and subjected to FACScan
analysis.15
Ac-LDL was radiolabeled with 125I by the iodine monochloride method.19 THP-1 cells (2 to 3x105) were preincubated with lipoprotein-deficient medium for 30 minutes at 37°C, and 125I–Ac-LDL was added at 4 to 5 µg/mL (in triplicate) for 24 to 72 hours at 37°C. A 50-fold excess of unlabeled Ac-LDL was added to every third sample to determine nonspecific uptake and degradation of 125I–Ac-LDL.20 The remaining cells were lysed with 0.1N NaOH, and total cell protein content was determined.17
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Results |
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-IFN Induces SR-A Expression During Early
Differentiation of MonocytesSR-A mRNA levels were determined by RT-PCR with the use of primers corresponding to exons 1 to 3, which are common to both isoforms of SR-A.15 As reported previously,9 13 SR-A mRNA expression was markedly enhanced in PMA-differentiated THP-1 monocytes compared with untreated controls (Figures 1A
and 2A). Addition of -IFN resulted in a
significant increase (P<0.01)
of SR-A expression compared with PMA-activated cells
(Figures 1A and 2B) and was most pronounced (4-fold) at
earlier time points (6 to 12 hours). When THP-1 monocytes were
preincubated with PMA for various times (6 to 144 hours) followed by
-IFN incubation for an additional 24 hours, SR-A expression
increased only 2.0- to 2.5-fold during the early stages of PMA
activation (P<0.01 at 6 hours)
and decreased after prolonged incubation with PMA
(Figure 1B).
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–), with PMA (–•–), with 
–), or with PMA + 
–) for 0 to 48 hours. SR-A and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA levels were determined. (B) THP-1 monocytes were preincubated with PMA for 0 to 144 hours before addition of
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Differential Stimulation of SR-A Isoforms in
-IFN–Activated Monocytes
-IFN–inducible expression of SR-A during early
monocyte differentiation was confirmed by Northern blotting
(Figure 2
). During the first 48 hours of PMA activation, a
constant increase of the dominantly expressed SR-AII, as well as the
SR-AI isoform, was observed
(Figure 2A, lanes 1 through 3). In contrast, PMA incubation
for 4 to 7 days reduced SR-AI and SR-AII expression levels 1.5- and
2-fold, respectively, compared with 24-hour PMA-activated THP-1
cells
(Figure 2A; compare lane 3 with lanes 4 and 5). Addition of
-IFN after 6 hours of PMA preincubation resulted in a 2-fold
increase of SR-AII mRNA levels after 24 hours
(Figure 2B, lane 3), whereas prolonged -IFN exposure
resulted in a strong decrease in SR-A mRNA levels
(Figure 2B, lane 4; also see
Figure 2C, lane 5).
-IFN–induced SR-A mRNA expression peaked after 12-hour
preincubation with PMA
(Figure 2C, lane 3), similar to the results obtained from
RT-PCR analysis (see
Figure 1B) and indicating that maximum -IFN–mediated
SR-A induction occurs within the first 12 hours of PMA activation. In
contrast, prolonged PMA prestimulation resulted in a -IFN–mediated
repression of both SR-AI and SR-AII mRNA levels
(Figure 2C, lanes 4 and 5). Because the duration of PMA
incubation mimics the differentiation status of THP-1 cells, our
results suggest that the time-related effects on total SR-A expression
reflect the sum of differential -IFN responses on each SR-A mRNA
isoform in early and later stages of monocyte
maturation.
-IFN Induces SR-A Expression During
Maturation of Blood-Derived Monocytes
Human blood–derived monocytes (n=12) were
analyzed to confirm the potential relevance of -IFN
signaling on SR-A expression during blood monocyte maturation
(Figure 3). Owing to the variation in SR-A expression among
monocytes from different
subjects,15 SR-A mRNA
increased by 8.5- to 22-fold during maturation of macrophages,
depending on the individual analyzed. In contrast and similar
to previous findings,10
prolonged incubations with -IFN of more mature macrophages
resulted in SR-A mRNA expression levels that were reduced by 43% to
80% compared with the respective control macrophages
analyzed (P=0.01).
These results are correlated with the data obtained from
PMA-activated THP-1 monocytes (see
Figure 1) and indicate that -IFN exerts opposite effects
on SR-A expression during early versus late stages of blood monocyte
maturation.
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–; No. 4: –
–; No. 5: 
). After 6, 24, 48, and 96 hours, mRNA levels of SR-A and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were determined simultaneously by fluorescent RT-PCR as described. Relative SR-A expression was calculated as the ratio of SR-A and GAPDH peak areas. The relative induction of SR-A expression for each individual is given as the difference of SR-A expression with and without
Induction of SR-A Activity in
-IFN–Activated THP-1 Monocytes
To determine that upregulation of SR-A mRNA
corresponded to increased SR-A receptor activity, we measured lipid
accumulation and Ac-LDL degradation in -IFN–activated and
PMA-treated THP-1 monocytes
(Table 1). -IFN activation of PMA-differentiated THP-1
monocytes showed an almost 2-fold increase in cholesteryl ester content
after lipid loading
(Table 1A; 88.6±10.4 nmol cholesteryl ester–derived
cholesterol per mg cell protein;
P=0.03), a 2-fold increase in
DiI–Ac-LDL accumulation
(Table 1B), and a 1.5-fold increase in
125I–Ac-LDL degradation
(Table 1C; 154.9±26.7 ng/mg cell protein;
P=0.02) compared with
PMA-induced controls. These results indicate that -IFN–induced SR-A
mRNA expression leads to elevated SR-A activity during the early stages
of monocyte differentiation.
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Expression of Other -IFN–Inducible Genes in
THP-1 Monocytes
To compare the -IFN–regulated SR-A expression
pattern with other well-known -IFN–responsive genes, we examined
the expression of STAT1 and IP-10, a STAT1-responsive
gene14 (see Figure I at
http://www.ahajournals.org). In these experiments, the
-IFN–inducible expression patterns of STAT1 and IP-10 in THP-1
and blood-derived monocytes were similar to the SR-A expression
analysis described above and indicated that comparable
transcriptional mechanisms are involved in the regulation of these
genes.
Identification of a Potential STAT1 Binding
Element in the SR-A Promoter
The observed expression pattern of SR-A
(Figures 1 through 3) and the increased STAT1 binding
activity in -IFN–activated THP-1
monocytes14 suggested the
presence of potential STAT1 binding sites (GAS) in the 5' regulatory
region of the human SR-A gene. We identified 2 putative GASs, located
-125 to -133 (SR-Ap) and -805 to -813 (SR-Ad) upstream from the
transcriptional SR-A initiation site, and performed gel retardation
assays with nuclear extracts from THP-1 cells and human blood–derived
monocytes
(Figure 4). The SR-Ad oligonucleotide did not
demonstrate -IFN–inducible binding of proteins (data not shown). In
contrast, extracts from PMA-activated THP-1 monocytes showed
-IFN–inducible binding activity to the STAT1 recognition site SR-Ap
(Figure 4A; compare lanes 4 and 5). This -IFN–inducible
binding activity was competed efficiently at all time points
analyzed by the human GTP-binding protein and IP-10
STAT114 binding elements
(Figure 4A, lanes 1 and 2 at t=9 hours). Binding activity
peaked after 12 hours
(Figure 4A, lane 6), whereas prolonged incubation with
-IFN resulted in reduced binding
(Figure 4A, lanes 7 and 8). Nuclear extracts from
blood-derived monocytes also demonstrated -IFN–inducible binding at
the early stages of maturation only
(Figure 4B). These results indicate that -IFN–inducible
STAT1 binding to the SR-Ap GAS in the SR-A promoter can occur during
both THP-1 cell and blood monocyte
differentiation.
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Differential Regulation of the SR-A Promoter in
-IFN–Activated Monocytes
THP-1 cells were transfected with a human SR-A
promoter–luciferase fusion construct including both the putative GAS
and AP-1 sites (pSRA-290) or a deletion mutant containing the AP-1 site
only (pSRA-116)
(Figure 5). Overnight incubation of transfected
PMA-activated THP-1 monocytes with -IFN resulted in a
3.1-fold induction of transcriptional activity of the 290-bp SR-A
promoter compared with PMA-activated controls
(Figure 5; P<0.01).
Deletion of the putative SR-Ap GAS in the SR-A promoter construct
pSRA-116 led to a complete loss of -IFN response after PMA
activation. In contrast, but in agreement with other
findings,10 11
transfection of the 290-bp SR-A promoter–luciferase fusion construct
followed by prolonged (3-day) incubation with -IFN resulted in a
3.9-fold reduction of luciferase expression compared with PMA controls
(data not shown). Taken together, these data strongly indicate that
-IFN–induced STAT1 binding to the proximal SR-A promoter region is
in part responsible for the increased SR-A expression in
PMA-differentiated THP-1 monocytes.
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Discussion |
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A number of cytokines have been shown to regulate SR-A expression and activity in vitro.8 9 10 11 12 13 The presence of
-IFN–secreting T lymphocytes in atherosclerotic
lesions21 and the important
role of -IFN for monocyte activation have resulted in several
studies that have analyzed the effect of -IFN on SR-A
expression in macrophages. In those experiments, prolonged
incubation of PMA-differentiated THP-1 macrophages or mature
primary macrophages with -IFN resulted in the downregulation
of SR-A expression, followed by reduced Ac-LDL binding and
internalization.10 11
In this study, we have demonstrated that -IFN can exert
opposite effects on SR-A expression, depending on the differentiation
status of monocytes and the duration of -IFN activation. SR-A mRNA
expression was increased after a 24-hour -IFN activation of THP-1
monocytes preincubated with PMA for 6 to 12 hours. Results from
-IFN–activated (<48 hours) human blood–derived monocytes
confirm these observations and can be correlated with the increased
Ac-LDL degradation of human macrophages after a 22-hour
incubation with -IFN.22
The dominantly expressed SR-AII mRNA isoform seems responsible for the
-IFN–induced SR-A activity in -IFN– and PMA-activated
THP-1 monocytes compared with controls.
Similar to previous
findings,10 11
-IFN was discovered to inhibit SR-A expression in mature
blood-derived macrophages but does not stimulate SR-A mRNA
levels in THP-1 cells after prolonged PMA activation. The complex
response in SR-A expression after short- versus long-term exposure to
-IFN cannot be explained by a transcriptional mechanism only.
-IFN–mediated stimulation of SR-A, affecting predominantly the
SR-AII isoform, could reflect functional specificities of the 2
isoforms in acute and chronic exposure to -IFN. Furthermore, the
diminution of SR-A expression after chronic -IFN exposure could be
attributable in part to an mRNA-destabilizing effect similar to the
tumor necrosis factor-–mediated posttranscriptional inhibition of
SR-A expression in THP-1
cells.13
The potential STAT1 binding site, located at positions
-125 to -133 of the SR-A promoter, demonstrated -IFN–inducible
binding of nuclear proteins. This binding is correlated with
-IFN–inducible expression of the endogenous SR-A gene
and activation of the SR-A promoter reporter gene construct. These
findings coincide with maximal induction of the -IFN receptor in
PMA-activated THP-1 cells under these
conditions,23 demonstrating
an enhanced capacity of monocytes to respond to -IFN. Our results
strongly suggest that STAT1 binding to the SR-A promoter is partly
responsible for -IFN–mediated activation of the SR-A promoter.
Although transcriptional activation by AP-1 is thought to be inhibited
by STAT1, we did not observe reduced binding of AP-1 to the SR-A
AP-1/ets motif after -IFN
activation during early monocyte maturation (data not shown). These
findings suggest that the basal AP-1 activity-dependent transcriptional
machinery is not negatively affected by STAT1 activation after a short
-IFN incubation. The -IFN– and PMA-inducible expression of an
SR-A promoter–luciferase fusion construct confirms these observations
and indicates that adjacent
AP-1/ets and STAT1 binding
sites on the SR-A promoter may cooperate to induce SR-A expression in
early differentiating monocytes. To the contrary, and as shown
previously,11 prolonged
-IFN exposure leads to inhibition of
AP-1/ets transcription factors,
which results in reduced SR-A promoter activity in mature
macrophages.
The opposite effects of -IFN on SR-A expression
during early versus late stages of monocyte maturation could explain
some of the conflicting results obtained from studies on the potential
role of -IFN in the pathogenesis of atherosclerosis.
Decreased SR-A expression in mature
macrophages10 11
and inhibition of smooth muscle cell
proliferation24 could
reflect the antiatherogenic properties of -IFN. Conversely, -IFN
potentiates atherosclerosis in apoE-knockout
mice25 and stimulates
vascular cell adhesion molecule-1 expression in rabbit aortic
endothelium.26
A critical step in the initiation of atherosclerosis is
the recruitment of monocytes to the arterial
wall.27 Therefore, the
stimulatory effect of -IFN on SR-A expression could indicate that
SR-A might not function as a lipoprotein receptor during the early
stages of monocyte differentiation but rather as an adhesion molecule,
as proposed by Fraser and
coworkers.28
-IFN–inducible STAT1 activity in the promoter of the intercellular
adhesion molecule-1 gene stimulates adhesion of
monocytes29 and suggests a
similar role of STAT1 for SR-A regulation and function. Future
experiments should be carried out to investigate SR-A’s function as
part of a general STAT1-mediated transcriptional mechanism to induce
adhesion of monocytes and promote their differentiation to
macrophages.
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Acknowledgments |
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This work was funded by the Medical Research Council/Novartis Canada/University Industry program (UI-11407) and La Succession J.A. DeSève. Thomas Grewal was supported by the Deutsche Forschungsgemeinschaft (DFG). We thank Dr Anne Minnich (Aventis) for helpful discussions. We are grateful to A. Chamberland, C. Lefevre, and J. Lavigne for excellent technical assistance.
Received January 10, 2001; accepted February 16, 2001.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Gerrity RG. The role of the monocyte in atherogenesis, I: transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981;103:181–190.[Abstract]
2.
Goldstein JL, Ho
YK, Basu SK, Brown MS. Binding site on macrophages that
mediates uptake and degradation of acetylated low density
lipoprotein producing massive cholesterol deposition.
Proc Natl Acad Sci
U S A. 1979;76:333–337.
3. Suzuki H, Kurihara Y, Takeya M, Kamada N, Kataoka M, Jishage K, Sakaguchi H, Kruijt J, Higashi T, Suzuki T, et al. A role of macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997;386:292–295.[Medline] [Order article via Infotrieve]
4.
Geng Y, Kodama T,
Hannson GK. Differential expression of scavenger receptor isoforms
during monocyte-macrophage differentiation and foam cell
formation. Arterioscler Thromb. 1994;14:798–806.
5.
Matsumoto A, Naito
M, Itakura H, Ikemoto S, Asaoka H, Hayakawa I, Kanamori H, Aburatani H,
Takaku F, Suzuki H, Kobari Y, Miyai T, Takahashi K, Cohen EH, Wydro R,
Housman DE, Kodama T. Human macrophage scavenger receptors:
primary structure, expression, and localization in atherosclerotic
lesions. Proc Natl Acad Sci
U S A. 1990;87:9133–9137.
6. Ashkenas J, Penman M, Vasile E, Acton S, Freeman M, Krieger M. Structures and high and low affinity ligand binding properties of murine type I and type II macrophage scavenger receptors. J Lipid Res. 1993;34:983–1000.[Abstract]
7.
DeVilliers WJS,
Fraser IP, Hughes DA, Doyle AG, Gordon S.
Macrophage-colony-stimulating factor selectively enhances
macrophage scavenger receptor expression and function.
J Exp Med. 1994;180:705–709.
8.
Moulton KS, Semple
K, Wu H, Glass CK. Cell-specific expression of the macrophage
scavenger receptor gene is dependent on PU.1 and a composite AP-1/ets
motif. Mol Cell Biol. 1994;14:4408–4418.
9.
Wu H, Moulton K,
Horvai A, Parik S, Glass CK. Combinatorial interactions between AP-1
and ets domain proteins
contribute to the developmental regulation of the macrophage
scavenger receptor. Mol Cell
Biol. 1994;14:2129–2139.
10.
Geng Y, Hansson
GK. Interferon- inhibits scavenger receptor expression and foam cell
formation in human monocyte-derived macrophages.
J Clin Invest. 1992;89:1322–1330.
11.
Horvai AE, Xu L,
Korzus E, Brard G, Kalafus D, Mullen TM, Rose DW, Rosenfeld MG, Glass
CK. Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and
p300. Proc Natl Acad Sci
U S A. 1997;94:1074–1079.
12.
Bottalico LA,
Wagner RE, Agellon LB, Assoian RK, Tabas I. Transforming growth
factor-ß1 inhibits scavenger receptor activity in THP-1 human
macrophages. J
Biol Chem. 1991;266:22866–22871.
13.
Hsu HY, Nicholson
AC, Hajjar DP. Inhibition of macrophage scavenger receptor
activity by tumor necrosis factor- is transcriptionally and
post-transcriptionally regulated. J
Biol Chem. 1996;271:7767–7773.
14.
Grewal T,
Boudreau M, Roy M, Chamberland A, Lefebvre C, Lavigne J, Davignon J,
Minnich A. Expression of -IFN responsive genes in scavenger receptor
overexpressing monocytes is associated with xanthomatosis.
Atherosclerosis. 1998;138:335–345.[Medline]
[Order article via Infotrieve]
15. Giry C, Giroux LM, Roy M, Davignon J, Minnich A. Characterization of inherited scavenger receptor overexpression and abnormal macrophage phenotype in a normolipidemic subject with planar xanthoma. J Lipid Res. 1996;37:1422–1435.[Abstract]
16.
Emi M, Asoaka H,
Matsumoto A, Itakura H, Kurihara Y, Wada Y, Kanamori H, Yazaki Y,
Takahashi E, Lepert M, Lalouel JM, Kodama T, Mukai T. Structure,
organization, and chromosomal mapping of the human macrophage
scavenger receptor gene. J Biol
Chem. 1993;268:2120–2125.
17. Markwell MK, Haas SM, Tolbert NE. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem. 1978;87:206–210.[Medline] [Order article via Infotrieve]
18. Innerarity TL, Pitas RE, Mahley RW. Metabolism of plasma lipoproteins. In: Albers JJ, Seghrest JP, eds. Methods in Enzymology: Lipoprotein-Receptor Interactions. New York, NY: Academic Press; 1986;129:542–565.
19. McFarlane AS. Efficient trace labeling of proteins with iodine. Nature. 1958;182:53–57.[Medline] [Order article via Infotrieve]
20. Im MJ, Dawes J, Jessup W. Transendothelial transport of modified low density lipoproteins. Atherosclerosis. 1994;108:5–17.[Medline] [Order article via Infotrieve]
21. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809.[Medline] [Order article via Infotrieve]
22.
Lopes-Virella MF,
Klein RL, Stevenson HC. Low density lipoprotein metabolism
in human macrophages stimulated with microbial-related
products.
Arteriosclerosis. 1987;7:176–184.
23.
Mao C, Merlin G,
Balotti R, Metzler M, Aguet M. Rapid increase of the human IFN-
receptor phosphorylation in response to human IFN-
and phorbol myristate acetate: involvement of different
serine/threonine kinases. J
Immunol. 1990;145:4257–4264.[Abstract]
24.
Hansson GK,
Hellstraand M, Rymo L, Rubbia L, Gabbiani G. Interferon- inhibits
smooth muscle cell proliferation and expression of
differentiation-specific -smooth muscle actin in
arterial smooth muscle cells.
J Exp Med. 1989;170:1595–1608.
25.
Gupta S, Pablo
AM, Jiang XC, Wang N, Tall AR, Schindler C. IFN- potentiates
atherosclerosis in ApoE knock-out mice.
J Clin Invest. 1997;99:2752–2761.[Medline]
[Order article via Infotrieve]
26.
Li H,
Cybulsky MI, Gimbrone MA, Libby P. An atherogenic diet rapidly induces
VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion
molecule, in rabbit aortic endothelium.
Arterioscler Thromb. 1993;13:197–204.
27.
Smith JD, Trogan
E, Ginsberg M, Grigaux C, Tian J, Miyata M. Decreased
atherosclerosis in mice deficient in both
macrophage-colony stimulating factor (op) and apolipoprotein E.
Proc Natl Acad Sci
U S A. 1995;92:8264–8268.
28. Fraser I, Hughes D, Gordon S. Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Nature. 1993;164:343–346.
29.
Coccia EM, Del
Russo N, Stellaci E, Testa U, Marziali G, Battistini A. STAT1
activation during monocyte to macrophage maturation: role of
adhesion molecules. Int
Immunol. 1999;11:1075–1083.
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