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CHEMOKINES
From INSERM U479, Faculté Bichat, Paris, France;
CNRS UMR 7627, Laboratoire d'Immunologie Cellulaire et Tissulaire,
Hôpital Pitié-Salpêtrière, Paris, France;
Service de Nutrition Humaine, Faculté Bichat, Paris, France;
Service de Cardiologie, CHU Bichat, Paris, France; Laboratory of Host
Defenses, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Bethesda, MD, USA; and Service
d'Hématologie Biologique et Immunologie, Hôpital Louis
Mourier AP-HP, Colombes, France.
Coronary atherosclerosis is a major cause of death in
industrialized countries. Monocytes, which play a key role in
atherosclerosis, migrate into the vessel wall, presumably guided by
specific chemoattractant and adhesion molecules. A compelling
candidate for this role is the chemokine receptor CX3CR1, which is
expressed on monocytes and acts as either a chemotactic receptor or an
adhesion molecule, depending on whether its ligand, fractalkine, is
presented free or membrane bound. A common variant of CX3CR1 was
recently identified, encoded by the alleles I249 and M280, which form a
common I249M280 haplotype. When CX3CR1
genotypes were analyzed in 151 patients with acute coronary syndromes
and in 249 healthy controls, CX3CR1 I249 heterozygosity was associated
with a markedly reduced risk of acute coronary events, independent of
established acquired coronary risk factors (eg, smoking, diabetes). The
adjusted odds ratio for this allele was 0.43 (95% confidence interval,
0.26-0.72; P = .001). Consistent with this, functional
analysis of peripheral blood mononuclear cells showed that CX3CR1 I249
heterozygosity was associated with a significant decrease in the number
of fractalkine binding sites per cell. The results show that CX3CR1
I249 is an independent genetic risk factor for coronary artery disease
and that CX3CR1 may be involved in the pathogenesis of atherosclerotic disease.
(Blood. 2001;97:1925-1928) It is now widely accepted that inflammatory
pathways play a major role in the pathogenesis of atherosclerosis. In
particular, monocyte/macrophage accumulation and activation in the
vessel wall appear to be critical events, not only during the initial phase of plaque formation,1 but also in chronic lesion
progression and during acute complications such as plaque rupture and
thrombosis.2 The molecular mechanisms responsible for
monocyte accumulation in plaque are likely to include chemokines and
their receptors because these molecules are major regulators of
specific leukocyte trafficking. The CX3C chemokine fractalkine (FKN)
and its 7-transmembrane domain G-protein-coupled receptor CX3CR1 are
particularly compelling candidates. FKN is a unique chemokine because
it exists in both a soluble form and in a membrane-anchored form, for
example on the surface of interleukin-1-activated and tumor necrosis
factor-activated endothelium.3 Membrane-bound FKN
directly mediates the capture and firm adhesion of CX3CR1-expressing
leukocytes, thus providing a novel pathway for leukocyte
activation.4 Soluble FKN has leukocyte
chemotactic activity.
Recently, we identified 2 common single-nucleotide polymorphisms
in the open reading frame of CX3CR1. The polymorphisms are nonsynonymous substitutions causing relatively conservative amino acid
changes (V249I and T280M; single-letter amino acid code) in the CX3CR1
protein. The 2 polymorphisms are in strong linkage disequilibrium,
forming a common I249M280
haplotype.5 It is interesting that functional CX3CR1
analysis showed that FKN binding was reduced in peripheral blood
mononuclear cells (PBMCs) from patients with human immunodeficiency
virus (HIV) homozygous for the I249M280
haplotype. Here we report that allele I249 is associated with a reduced
risk of acute coronary artery disease as well as altered CX3CR1
expression and ligand-binding affinity.
Subjects
Screening for polymorphisms
Receptor binding assay Binding experiments were carried out using 125I-FKN (specific activity = 2200 Ci/mmol protein; Amersham, Saclay, France). PBMCs were isolated from heparinized venous blood from healthy volunteers by one-step centrifugation on a Ficoll separating solution (Biochrom KG, Berlin, Germany). One million PBMCs were incubated in duplicate with increasing amounts of 125I-labeled FKN (0.02-2 nM) in the presence or absence of a 500-fold excess of unlabeled recombinant human FKN (TEBU, Le Perray en Yvelines, France) in Hanks' buffered salt solution (HBSS; Life Technologies, Cergy Pontoise, France) containing 1 mg/mL bovine serum albumin and 0.01% azide, pH 7.4, in a total volume of 200 µL. After incubation for 2 hours at 37°C, unbound chemokine was separated from cells by washing with 1 mL HBSS containing 10% sucrose; emissions were then counted
in the cell pellet. Nonspecific binding represented less than 10% of
total binding and was subtracted from total binding to define specific
FKN binding.
Statistical analysis The Hardy-Weinberg equilibrium was tested using a 2 test with 1 degree of freedom. A logistic regression
analysis was performed with Systat statistical software (SPSS, Chicago,
IL) to determine the association of the genotypes with acute
coronary events after accounting for sex, age, smoking, and other risk
factors (hypercholesterolemia, diabetes mellitus, hypertension, and
obesity). The genotype was included in the equation as a 2-class
variable (ie, carrying or not carrying the I allele, coded 0 or 1) or
as a 3-class variable corresponding to the 3 genotypes (coded 1, 2, and
3). Interactions between risk factors and genotypes were also tested by
logistic regression. Binding parameters (Bmax and
Kd) were compared between genotypes using analysis
of variance (performed between the groups carrying the VV, VI, and II
genotypes), followed by the protected least significant difference
Fisher test. Results are expressed as mean ± SEM.
The 151 patients (134 with MI and 17 with UA) and 249 controls
were well matched in terms of age and sex (Table
1). All of the subjects were white. As
expected, risk factors for coronary heart disease (including current
smoking, hypercholesterolemia, diabetes mellitus, hypertension, and
obesity) were more frequent among cases than among controls
(P < .005).
The frequencies of the V249I and T280M polymorphisms showed no
deviation from Hardy-Weinberg equilibrium. However, a statistically significant difference in genotype frequencies was observed in cases
compared with controls. The adjusted odds ratios (ORs) associated with
the presence of the M280 (TM + MM versus TT genotype) and I249
alleles (VI + II versus VV genotype) were 0.49 (95% confidence interval [CI], 0.27-0.89; P = .002) and 0.43 (95% CI,
0.26-0.72; P = .001), respectively (Table
2). Thus, these alleles were associated with a reduced risk of acute coronary events. To calculate the OR for
each genotype carrying the I249 or M280 allele, we also tested the
genotype as a 3-class variable. The adjusted ORs were 0.47 (95% CI,
0.26-0.88; P < .02) and 0.68 (95% CI, 0.09-5.45; P = .7) for the TM and MM genotypes, respectively; they
were 0.44 (95% CI, 0.26-0.75; P = .003) and 0.39 (95%
CI, 0.13-1.19; P = .099) for the VI and II genotypes,
respectively. As shown recently,5 the T280M and V249I
polymorphisms are in complete linkage disequilibrium and generate 6 combined genotypes of the 9 theoretically possible (Table
3) and only 3 haplotypes
(V249T280, I249T280,
and I249M280). Indeed, all subjects
carrying allele M280 also carry allele I249, whereas in some subjects,
allele I249 is associated with allele T280. However, when the T280M
polymorphism was used in the same logistic equation as the V249I
polymorphism, only the effect of the I249 allele remained significant:
Adjusted ORs were 0.84 (95% CI, 1.84-0.39; P = .669) and
0.48 (95% CI, 0.92-0.25; P = .028) for the M280 and I249
alleles, respectively. Therefore, we considered that the protective
effect was due to the I249 allele and performed subsequent calculations
using the V249I genotypes. No significant interaction was found between
genotype and any of the adjustment variables (sex, age, smoking, and
other risk factors) when adding interaction terms in the logistic
regression.
It is important to consider potential mechanisms whereby CX3CR1 could
alter predisposition to cardiovascular disease. PBMCs from 27 healthy
donors of defined genotypes were tested for FKN binding capacities.
From the saturation binding curves (data not shown), we used a
nonlinear regression to extrapolate the total number of FKN binding
sites (Bmax) and the apparent binding affinity of FKN to
PBMCs (Kd) (Figure 1). The
binding parameters for individuals with the reference VV genotype
appeared more homogeneous than those of the other genotypes. The
analysis also revealed a significantly reduced Bmax (Figure
1A) when comparing the reference genotype (20 090 ± 1290 sites per
PBMC, n = 11) with the VI genotype (12 850 ± 1826 sites per PBMC,
n = 13, P < .02). The Bmax values of the
VI-TT genotype (12 880 ± 2827 sites per PBMC, n = 8) and VI-TM genotype (12 810 ± 1911 sites per PBMC, n = 5) were similar.
Furthermore, Figure 1B shows that the Kd was significantly
decreased when comparing PBMCs from individuals with the VV genotype
(163 ± 14 pM, n = 11) and with the VI genotype (111 ± 15 pM,
n = 13, P < .02). The Kd values of the
VI-TT subgroup (104 ± 21.2 pM, n = 8) and the VI-TM subgroup
(121 ± 19.3 pM, n = 5) did not differ significantly. These results
show that, compared with PBMCs from homozygous VV individuals, PBMCs
from heterozygous VI individuals expressed 35% fewer receptors at the
cell surface, with an affinity increased by about 30%. Only 3 individuals homozygous for the I249 allele were analyzed, and the
binding parameters were highly heterogeneous (16 830 ± 7813 sites
per PBMC), with an apparent affinity of 174 ± 21 pM. Thus, a larger
study will be needed to accurately compare FKN binding parameters of
these individuals with those of other CX3CR1 genotypes.
Our results show that the CX3CR1 I249 allele is associated with a markedly reduced risk of acute coronary events independent of established coronary risk factors. The epidemiologic data correlated with altered FKN binding by PBMCs from I249 heterozygous individuals. The V249I and T280M polymorphisms, located in the sixth and seventh transmembrane domains of the CX3CR1 protein, respectively, are the first genetic tools for studying the specific role of CX3CR1 in human disease. We previously reported that the CX3CR1 M280 allele was associated with accelerated onset of acquired immunodeficiency syndrome among HIV seroconverters from the SEROCO cohort in France (relative risk = 2.44, P = .016), whereas the I249 allele was not associated with altered HIV disease progression.5 Although the mechanism is not known, it is noteworthy that CX3CR1 has been reported to function in vitro with CD4 as an HIV coreceptor and that the M280 allele is associated with reduced receptor expression on PBMCs from HIV-positive subjects.8 In contrast to HIV, in which accelerated disease progression was restricted to M280 homozygotes, the association of CX3CR1 with acute coronary disorders was noted only for I249 and for heterozygotes. This suggests different effects of the 2 polymorphisms on CX3CR1 function. Our study may have lacked sufficient power to detect an association of M280 with acute coronary disease. A larger study will be necessary to determine disease risk in T280 homozygous subjects who carry the I249 allele alone (II-TT individuals) and to determine whether any supplementary risk is associated with allele M280 in subjects who also carry allele I249 (II-MM individuals). To test how CX3CR1 polymorphism may affect the risk of acute coronary disease, we examined FKN binding and found that FKN binding-site density on PBMCs from individuals carrying VI genotypes (either VI-TT or VI-TM) was approximately 40% lower (decreased Bmax) than on PBMCs from individuals bearing the reference genotype VV-TT. This would be expected to reduce monocyte adhesion to injured endothelium, and therefore this is a potential mechanism for the reduced risk of acute coronary events associated with this genotype. This hypothesis implies that the small increase (approximately 2-fold) in FKN binding affinity (decreased Kd) for PBMCs observed for I249 heterozygotes has a negligible effect on adhesive and chemotactic function of CX3CR1, which is reasonable because large effects of binding affinity on receptor occupancy will be restricted to a very narrow concentration range of ligand. The binding phenotype of PBMCs from VI heterozygotes is consistent with our previous study of 4 HIV-positive II homozygotes (II-MM compound genotype), in whom FKN binding-site density on PBMCs was only 20% of that of HIV-positive VV-TT controls. In that study, PBMCs from 2 individuals with II-TT compound genotypes also had a reduced FKN binding-site density; however, the difference did not reach statistical significance. In the present study of healthy donors, FKN binding levels on PBMCs from 3 individuals with II-containing compound genotypes were highly variable and not significantly different from those of VV-TT controls. In addition, the binding affinities fell within a narrow range from a 2-fold increase to 3-fold decrease for PBMCs from II-containing compound genotypes in the 2 studies. Further work will be needed to more accurately define FKN binding parameters and FKN function using both primary cells from individuals with these relatively uncommon compound CX3CR1 genotypes, as well as cell lines expressing cloned receptor variants. It will also be important to test whether these alleles are linked to promoter polymorphisms that may alter receptor expression independent of receptor structure. Ultimately, in vivo models may define the importance of CX3CR1 in atherosclerosis. Recently, CX3CR1-deleted mice have been generated. These animals were viable and fertile and had no spontaneous specific phenotype.9 Placing the CX3CR1-deleted mice in conditions leading to cardiovascular disease may reveal the importance of CX3CR1 in atherosclerosis. Such experiments have already demonstrated a significant role of the monocyte-targeted chemokine monocyte chemoattractant protein-1 (MCP-1) and its specific receptor CCR2 in mouse models of atherogenesis.10 Consistent with this, expression of MCP-1 has been correlated with human coronary artery disease.11 Although many other monocyte-derived chemokine signaling pathways have also been defined and should be considered for potential roles in atherosclerosis, one major candidate protein is CX3CR1. In conclusion, this study demonstrates that the I249 allele of the CX3CR1 gene is associated with a reduced risk of acute coronary events. The underlying mechanism might involve less efficient interaction between monocytes and injured endothelium in subjects exposed to coronary risk factors, as a result of decreased expression of CX3CR1. These results suggest that agents blocking the FKN-CX3CR1 interaction might help to prevent the onset and progression of atherosclerotic lesions.
Submitted July 10, 2000; accepted December 7, 2000.
Supported by grant 2000005884 from the Fondation de France. S.F. was a recipient of a fellowship from the French Agence Nationale de Recherche sur le SiDA.
D.M. and S.F. contributed equally to this work.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Dominique de Prost, Service d'Hématologie Biologique et Immunologie, Hôpital Louis Mourier AP-HP, 178 rue des Renouillers, 92701 Colombes, France; e-mail: dominique.de-prost{at}lmr.ap-hop-paris.fr.
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J.-C. Gevrey, B. M. Isaac, and D. Cox Syk Is Required for Monocyte/Macrophage Chemotaxis to CX3CL1 (Fractalkine) J. Immunol., September 15, 2005; 175(6): 3737 - 3745. [Abstract] [Full Text] [PDF]
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 O. Quehenberger Thematic Review Series: The Immune System and Atherogenesis. Molecular mechanisms regulating monocyte recruitment in atherosclerosis J. Lipid Res., August 1, 2005; 46(8): 1582 - 1590. [Abstract] [Full Text] [PDF]
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E. Lavergne, J. Labreuche, M. Daoudi, P. Debre, F. Cambien, P. Deterre, P. Amarenco, C. Combadiere, and on Behalf of the GENIC Investigators Adverse Associations Between CX3CR1 Polymorphisms and Risk of Cardiovascular or Cerebrovascular Disease Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 847 - 853. [Abstract] [Full Text] [PDF]
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 M Hasegawa, S Sato, T Echigo, Y Hamaguchi, M Yasui, and K Takehara Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis Ann Rheum Dis, January 1, 2005; 64(1): 21 - 28. [Abstract] [Full Text] [PDF]
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 D. Teupser, S. Pavlides, M. Tan, J.-C. Gutierrez-Ramos, R. Kolbeck, and J. L. Breslow Major reduction of atherosclerosis in fractalkine (CX3CL1)-deficient mice is at the brachiocephalic artery, not the aortic root PNAS, December 21, 2004; 101(51): 17795 - 17800. [Abstract] [Full Text] [PDF]
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C. N. Davis, V. Zujovic, and J. K. Harrison Viral Macrophage Inflammatory Protein-II and Fractalkine (CX3CL1) Chimeras Identify Molecular Determinants of Affinity, Efficacy, and Selectivity at CX3CR1 Mol. Pharmacol., December 1, 2004; 66(6): 1431 - 1439. [Abstract] [Full Text] [PDF]
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I. F. Charo and M. B. Taubman Chemokines in the Pathogenesis of Vascular Disease Circ. Res., October 29, 2004; 95(9): 858 - 866. [Abstract] [Full Text] [PDF]
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E. Lavergne, C. Combadiere, M. Iga, A. Boissonnas, O. Bonduelle, M. Maho, P. Debre, and B. Combadiere Intratumoral CC Chemokine Ligand 5 Overexpression Delays Tumor Growth and Increases Tumor Cell Infiltration J. Immunol., September 15, 2004; 173(6): 3755 - 3762. [Abstract] [Full Text] [PDF]
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G. Ghilardi, M. L. Biondi, O. Turri, E. Guagnellini, and R. Scorza Internal Carotid Artery Occlusive Disease and Polymorphisms of Fractalkine Receptor CX3CR1: A Genetic Risk Factor Stroke, June 1, 2004; 35(6): 1276 - 1279. [Abstract] [Full Text] [PDF]
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M. Daoudi, E. Lavergne, A. Garin, N. Tarantino, P. Debre, F. Pincet, C. Combadiere, and P. Deterre Enhanced Adhesive Capacities of the Naturally Occurring Ile249-Met280 Variant of the Chemokine Receptor CX3CR1 J. Biol. Chem., May 7, 2004; 279(19): 19649 - 19657. [Abstract] [Full Text] [PDF]
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S. Y. Ahn, C.-H. Cho, K.-G. Park, H. J. Lee, S. Lee, S. K. Park, I.-K. Lee, and G. Y. Koh Tumor Necrosis Factor-{alpha} Induces Fractalkine Expression Preferentially in Arterial Endothelial Cells and Mithramycin A Suppresses TNF-{alpha}-Induced Fractalkine Expression Am. J. Pathol., May 1, 2004; 164(5): 1663 - 1672. [Abstract] [Full Text] [PDF]
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H. Umehara, E. T. Bloom, T. Okazaki, Y. Nagano, O. Yoshie, and T. Imai Fractalkine in Vascular Biology: From Basic Research to Clinical Disease Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 34 - 40. [Abstract] [Full Text] [PDF]
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A. D. Lucas, C. Bursill, T. J. Guzik, J. Sadowski, K. M. Channon, and D. R. Greaves Smooth Muscle Cells in Human Atherosclerotic Plaques Express the Fractalkine Receptor CX3CR1 and Undergo Chemotaxis to the CX3C Chemokine Fractalkine (CX3CL1) Circulation, November 18, 2003; 108(20): 2498 - 2504. [Abstract] [Full Text] [PDF]
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M. C. Grimm, R. Newman, Z. Hassim, N. Cuan, S. J. Connor, Y. Le, J. M. Wang, J. J. Oppenheim, and A. R. Lloyd Cutting Edge: Vasoactive Intestinal Peptide Acts as a Potent Suppressor of Inflammation In Vivo by Trans-Deactivating Chemokine Receptors J. Immunol., November 15, 2003; 171(10): 4990 - 4994. [Abstract] [Full Text] [PDF]
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A. Garin, N. Tarantino, S. Faure, M. Daoudi, C. Lecureuil, A. Bourdais, P. Debre, P. Deterre, and C. Combadiere Two Novel Fully Functional Isoforms of CX3CR1 Are Potent HIV Coreceptors J. Immunol., November 15, 2003; 171(10): 5305 - 5312. [Abstract] [Full Text] [PDF]
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J. Barlic, J. M. Sechler, and P. M. Murphy IL-15 and IL-2 oppositely regulate expression of the chemokine receptor CX3CR1 Blood, November 15, 2003; 102(10): 3494 - 3503. [Abstract] [Full Text] [PDF]
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E. Lavergne, B. Combadiere, O. Bonduelle, M. Iga, J.-L. Gao, M. Maho, A. Boissonnas, P. M. Murphy, P. Debre, and C. Combadiere Fractalkine Mediates Natural Killer-Dependent Antitumor Responses in Vivo Cancer Res., November 1, 2003; 63(21): 7468 - 7474. [Abstract] [Full Text] [PDF]
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C. Hundhausen, D. Misztela, T. A. Berkhout, N. Broadway, P. Saftig, K. Reiss, D. Hartmann, F. Fahrenholz, R. Postina, V. Matthews, et al. The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion Blood, August 15, 2003; 102(4): 1186 - 1195. [Abstract] [Full Text] [PDF]
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P. Dorfmuller, F. Perros, K. Balabanian, and M. Humbert Inflammation in pulmonary arterial hypertension Eur. Respir. J., August 1, 2003; 22(2): 358 - 363. [Abstract] [Full Text] [PDF]
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M. E. DeVries, H. Cao, J. Wang, L. Xu, A. A. Kelvin, L. Ran, L. A. Chau, J. Madrenas, R. A. Hegele, and D. J. Kelvin Genomic Organization and Evolution of the CX3CR1/CCR8 Chemokine Receptor Locus J. Biol. Chem., March 28, 2003; 278(14): 11985 - 11994. [Abstract] [Full Text] [PDF]
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C. Combadiere, S. Potteaux, J.-L. Gao, B. Esposito, S. Casanova, E. J. Lee, P. Debre, A. Tedgui, P. M. Murphy, and Z. Mallat Decreased Atherosclerotic Lesion Formation in CX3CR1/Apolipoprotein E Double Knockout Mice Circulation, February 25, 2003; 107(7): 1009 - 1016. [Abstract] [Full Text] [PDF]
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M. Nishimura, H. Umehara, T. Nakayama, O. Yoneda, K. Hieshima, M. Kakizaki, N. Dohmae, O. Yoshie, and T. Imai Dual Functions of Fractalkine/CX3C Ligand 1 in Trafficking of Perforin+/Granzyme B+ Cytotoxic Effector Lymphocytes That Are Defined by CX3CR1 Expression J. Immunol., June 15, 2002; 168(12): 6173 - 6180. [Abstract] [Full Text] [PDF]
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 K. Balabanian, A. Foussat, P. Dorfmuller, I. Durand-Gasselin, F. Capel, L. Bouchet-Delbos, A. Portier, A. Marfaing-Koka, R. Krzysiek, A.-C. Rimaniol, et al. CX3C Chemokine Fractalkine in Pulmonary Arterial Hypertension Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1419 - 1425. [Abstract] [Full Text] [PDF]
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A. Ludwig, T. Berkhout, K. Moores, P. Groot, and G. Chapman Fractalkine Is Expressed by Smooth Muscle Cells in Response to IFN-{gamma} and TNF-{alpha} and Is Modulated by Metalloproteinase Activity J. Immunol., January 15, 2002; 168(2): 604 - 612. [Abstract] [Full Text] [PDF]
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 C. Trebst and R. M. Ransohoff Investigating Chemokines and Chemokine Receptors in Patients With Multiple Sclerosis: Opportunities and Challenges Arch Neurol, December 1, 2001; 58(12): 1975 - 1980. [Abstract] [Full Text] [PDF]
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R. Wayne Alexander Cytokine Receptor CX3CR-1 and Fractalkine: New Factors in the Atherosclerosis Drama? Circ. Res., August 31, 2001; 89(5): 376 - 377. [Full Text] [PDF]
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K. J. Garton, P. J. Gough, C. P. Blobel, G. Murphy, D. R. Greaves, P. J. Dempsey, and E. W. Raines Tumor Necrosis Factor-alpha -converting Enzyme (ADAM17) Mediates the Cleavage and Shedding of Fractalkine (CX3CL1) J. Biol. Chem., October 5, 2001; 276(41): 37993 - 38001. [Abstract] [Full Text] [PDF]
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C.-L. Tsou, C. A. Haskell, and I. F. Charo Tumor Necrosis Factor-alpha -converting Enzyme Mediates the Inducible Cleavage of Fractalkine J. Biol. Chem., November 21, 2001; 276(48): 44622 - 44626. [Abstract] [Full Text] [PDF]
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D. H. McDermott, J. P.J. Halcox, W. H. Schenke, M. A. Waclawiw, M. N. Merrell, N. Epstein, A. A. Quyyumi, and P. M. Murphy Association Between Polymorphism in the Chemokine Receptor CX3CR1 and Coronary Vascular Endothelial Dysfunction and Atherosclerosis Circ. Res., August 31, 2001; 89(5): 401 - 407. [Abstract] [Full Text] [PDF]
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Top
Abstract
Introduction
50% diameter stenosis were selected. Two hundred
forty-nine age- and sex-matched controls were recruited among hospital
employees and blood donors. As expected, risk factors for coronary
heart disease (including current or recent smoking,
hypercholesterolemia, diabetes mellitus, hypertension, and obesity)
were more frequent among cases than controls.
), VI-TT (
), VI-TM (
), II-TT
(
), II-TM (
), and II-MM (
). Significance by analysis of
variance was P < .05 for the Bmax and the
Kd values. P values on the figure indicate the
significance of the comparison between VV and VI genotypes (protected
least significant difference Fisher test). Note that the
Bmax and Kd values reported here for the
reference genotype (more than10 000 sites per cell with an apparent
affinity of 100 pM) are different from those in our previous report
(2800 sites per cell with 12 pM affinity).
/