Eotaxin(CCL11) An Biomarker for obesity,
angiographic coronary artery disease & Asthma
EK-033-39;EK-033-40
Association of plasma eotaxin levels with the presence
and extent of angiographic coronary artery disease
Eotaxin (CCL11) is an eosinophil-specific
chemoattractant which has been found to be highly expressed
at sites of vascular pathology. In the present study, we aimed
to evaluate the association of plasma eotaxin levels with the
presence and extent of angiographic coronary artery disease
(CAD). Three hundred and fifty six consecutive patients attending
for elective coronary angiography were investigated. Compared
with 111 patients without CAD, 245 with CAD showed higher eotaxin
concentrations [median (interquartile range): 76.0 (56.3-103.0)pg/ml
versus 116.0 (80.5-162.0)pg/ml, respectively; P<0.001]. Importantly,
a significant Spearman correlation was found between eotaxin
levels and the extent score of coronary artery stenosis (r=0.449,
P<0.001). A stepwise increase in plasma levels of eotaxin
was also found depending on the number of >50% coronary stenosis:
median value 76.0pg/ml in CAD(-) subjects, 96.0pg/ml in 1-vessel
disease, 128.0pg/ml in 2-vessel disease, and 129.0pg/ml in 3-vessel
disease (P<0.001 for trend). After confounding variables
were controlled for, multiple stepwise regression analysis demonstrated
that plasma eotaxin was an independent predictor of angiographic
extent of CAD (beta=0.426, P<0.001). Our data suggest that
increased eotaxin levels are associated with the presence of
CAD and that circulating levels of this chemokine may reflect
the extent of coronary atherosclerosis.
Emanuele E, et al. Atherosclerosis. 2005 Aug 3; [Epub ahead
of print]
Eotaxin-3 and interleukin-5 pleural
fluid levels are associated with pleural fluid eosinophilia
in post-coronary artery bypass grafting pleural effusions
OBJECTIVES: The primary aim of this study
was to examine the association between pleural fluid (PF) eosinophilia,
and the PF and serum levels of interleukin (IL)-5, eotaxin-2,
eotaxin-3, and vascular cell adhesion molecule (VCAM)-1 in patients
with post-coronary artery bypass grafting (CABG) pleural effusions.
DESIGN: A prospective observational study. SETTING: A tertiary
teaching hospital. PATIENTS AND METHODS: Thirty-eight patients
with post-CABG pleural effusions were recruited into the study.
An effusion that contained at least 10% eosinophils was called
"eosinophilic." The PF and serum levels of the cytokines and
VCAM-1 were measured using an enzyme-linked immunosorbent assay.
RESULTS: (1) The number of PF eosinophils significantly correlated
with the number of blood eosinophils. (2) PF IL-5 levels were
significantly higher than the corresponding serum levels, and
there was a significant correlation between the PF and serum
IL-5 levels. PF IL-5 levels significantly correlated with the
PF eosinophil count, and serum IL-5 levels significantly correlated
with the number of blood eosinophils. (3) PF eotaxin-3 levels
were significantly higher than serum levels, and PF eotaxin-3
levels significantly correlated with the PF eosinophil count.
(4) PF VCAM-1 levels were significantly lower than the corresponding
serum levels, and PF VCAM-1 levels were significantly higher
in eosinophilic pleural effusions (EPEs) than in non-EPEs. CONCLUSION:
In patients with post-CABG pleural effusions, IL-5 and eotaxin-3
are produced preferentially in the pleural cavity, and they
are strongly associated with PF eosinophilia.
Kalomenidis I, et al. Chest. 2005 Jun;127(6):2094-100.
Vasudevan A. R. , et al. Journal of Clinical Endocrinology &
Metabolism. November 1, 2005 as doi:10.1210/jc.2005-1280
Ectopic expression of eotaxin and other cytokines/chemokines
in adipose tissue induces Th2 cell–dependent inflammation
in the lung. Eotaxin may influence homing of bone marrow–
derived eosinophils to the lung directly, or indirectly by increasing
Th2 type cytokines. In addition, eotaxin and cytokines produced
by adipose tissue may possibly directly influence airway hyperresponsiveness,
thereby leading to an increased prevalence and severity of asthma
symptoms in obese individuals. Abbreviations: IL, interleukin;
Th2, T helper type 2. Vasudevan A. R. , et al. Journal of Clinical
Endocrinology & Metabolism. November 1, 2005 as doi:10.1210/jc.2005-1280
Figure 1A. Eotaxin mRNA levels in mouse adipose tissue detected
by RNAse protection assay. Levels of eotaxin mRNA normalized to
levels of GAPDH are shown for male (n=6 per group) and female
mice (n=3 per group). *p<0.05 for obese mice (high-fat diet;
shaded bars) vs. lean mice (normal diet; open bars). Vasudevan
A. R. , et al. Journal of Clinical Endocrinology & Metabolism.
November 1, 2005 as doi:10.1210/jc.2005-1280
Figure 1B. Eotaxin protein levels in mouse serum detected by
ELISA. Eotaxin protein levels in mouse serum are shown for male
and female mice (n=6 per group). *p<0.05, **p<0.01 for obese
mice (high-fat diet; open bars) vs. lean mice (normal diet; shaded
bars). Vasudevan A. R. , et al. Journal of Clinical Endocrinology
& Metabolism. November 1, 2005 as doi:10.1210/jc.2005-1280
Figure 1C. Correlation between adipose mRNA levels and serum
protein levels of eotaxin in mice. Pearson's correlation (r=0.778;
p=0.0081) demonstrates a significant correlation between adipose
eotaxin mRNA levels and serum eotaxin levels in mice. Vasudevan
A. R. , et al. Journal of Clinical Endocrinology & Metabolism.
November 1, 2005 as doi:10.1210/jc.2005-1280
Schematic representation of eotaxin-induced, CCR3-mediated
eosinophil activation. Binding of eotaxins to CCR3 receptors
expressed on the eosinophil's surface causes: chemotaxis preceded
by actin polymerization and cell shape change; production of
reactive oxygen molecules; degranulation of ECP and EDN; LTC4
formation at lipid bodies; and vesicular transport-mediated
release of preformed IL-4. These eosinophil effector responses
could be blocked by CCR3 receptor antagonists (e.g., Met-RANTES)
and monoclonal antibodies to CCR3 and were initially triggered
by common signaling steps, including activation of Gi protein
and a rapid influx of Ca++. Subsequent activation of distinct
kinases has been identified to each phenomenon. In addition,
eotaxin binding to CCR3 can inhibit cell infection by HIV-1
and induces ligand-dependent receptor internalization, whose
signaling pathways are completely unknown but independent on
Gi activation or Ca++ influx. Definition of abbreviations: 5-lypoxigenase,
5-LO; eosinophil cationic protein, ECP; eosinophil-derived neurotoxin,
EDN; extracellular signal-regulated kinase, ERK; phosphatidylinositol
3-kinase, PI3; protein kinase C, PKC; pertussis toxin, PTX.
Christianne Bandeira-Melo, Anne Herbst, and Peter F. Weller
. Am. J. Respir. Cell Mol. Biol., Volume 24, Number 6, June
2001 653-657
(A) Nucleotide sequence and deduced amino
acid sequence of human clone 25 cDNA coding region. The underlined
amino acids correspond to the predicted signal sequence with
the arrowhead indicating the predicted signal peptidase cleavage
site. (B) Amino acid sequence alignment of the predicted mature
clone 25 protein with other human CC chemokines as well as guinea
pig and mouse eotaxin. Amino acid numbering is relative to clone
25, and amino acids identical to clone 25 are boxed. These sequence
data are available from GenBank under accession number U34780.
Ponath P. D. et al. J. Clin. Invest. Volume 97, Number 3, February
1996, 604-612
Northern analysis of ~ 2 µg of oligo-dT-selected RNA from various
human tissues. Blots were purchased from Clontech and hybridized
as described in Methods. After boiling in 0.5% SDS to remove specific
probe, the blots were rehybridized with a beta-actin control.
Ponath P. D. et al. J. Clin. Invest. Volume 97, Number 3, February
1996, 604-612
Photomicrographs of human nasal polyp (A and C) and adjacent
nasal mucosa (B and D). The polyp (A) is characterized by extensive
submucosal infiltration by eosinophils (arrowheads) and attenuation
of the overlying respiratory epithelium. Immunoperoxidase staining
of step sections of the polyp (C) with antieotaxin mAb 6H9 revealed
intense immunoreactivity to epithelium, endothelium lining venules
(v), eosinophils (arrows), mononuclear cells (arrowheads), and
spindle cells. In contrast, the adjacent respiratory tissue is
characterized by normal pseudostratified columnar epithelium and
no eosinophil infiltration (B), and immunostaining for eotaxin
shows only light constitutive immunoreactivity to epithelium and
submucosal mesenchymal cells (D). (A and B) Hematoxylin and eosin,
×1,450; (C and D) ABC-peroxidase technique with Mayer's hematoxylin,
×1,450.
Ponath P. D. et al. J. Clin. Invest. Volume 97, Number 3, February
1996, 604-612
Northern analysis of chemokine expression in the gastrointestinal
tract. Total RNA (20 µg) from various gastrointestinal segments
of wild-type 129 SvEv mice was electrophoresed and transferred
to a membrane that was hybridized under conditions of high stringency
with cDNA probes for murine eotaxin, MCP-1, MCP-2, MCP-3, MCP-5,
RANTES, and MIP-1, using methods described previously (17). Control
RNA is derived from the lungs of IL-4 transgenic Clara cell lung
in transgenic mice (39). Each lane represents RNA from a different
animal, except the lanes for the tongue and esophagus, which were
pooled from multiple animals. Autoradiographs were exposed for
1–2 days. The chemokine cDNA probes were described previously
(16), except for MCP-2, which has recently been cloned (M.N. Sarafi
and A.D. Luster, unpublished data). The ethidium bromide–stained
gel (EtBr) is also shown.
Mishra A., et al. J Clin Invest, June 1999, Volume 103, Number
12, 1719-1727
Correlation between PF eotaxin-3 levels and
PF eosinophil levels. =
EPEs; =
non-EPEs.
Kalomenidis I, et al. Chest. 2005 Jun;127(6):2094-100.
Whole lung and bronchoalveolar lavage BAL eotaxin/CCL11 levels
in Aspergillus fumigatus-sensitized wild-type (Eo+/+) mice at
various times after soluble A. fumigatus (Asp) allergen challenge.
Eotaxin/CCL11 levels were measured using specific ELISAs as described
in MATERIALS AND METHODS. Data are expressed as means ± SE; n
= 3 mice/group. * P 0.05, compared with levels measured before
(t = 0) the allergen challenge.
Schuh J. M. et al. Am J Physiol Lung Cell Mol Physiol 283: L198-L204,
2002;
Whole lung and BAL eotaxin/CCL11 levels in A. fumigatus-sensitized
Eo+/+ mice at various times after A. fumigatus conidia challenge.
Eotaxin/CCL11 levels were measured using specific ELISAs as described
in MATERIALS AND METHODS. Data are expressed as means ± SE; n
= 5 mice/group. Schuh J. M. et al. Am J Physiol Lung Cell Mol
Physiol 283: L198-L204, 2002; .
=
EPEs; 
=
non-EPEs. 
