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-Induced Galectin-9
Departments of
* Radiology,
Immunology and Immunopathology,
Perinatology and Gynecology, and
Endocrinology, Kagawa Medical University, Kagawa, Japan;
¶ Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan; and
|| First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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stimulation. On the one hand, IL-4, known
as a Th2 cytokine, did not affect the galectin-9 expression in HFL-1
cells. We further confirmed that IFN- up-regulated the expression of
galectin-9 in primary human dermal fibroblasts. Flow cytometric
analysis revealed that IFN- up-regulated surface galectin-9
expression on HFL-1 cells. Stimulation of HFL-1 cells with IFN-
up-regulated adhesion of eosinophils, but not neutrophils, to HFL-1
cells. This adherence of eosinophils to HFL-1 cells was inhibited by
both lactose and anti-galectin-9 Ab. These findings demonstrate
that IFN--induced galectin-9 expression in fibroblasts mediates
eosinophil adhesion to the cells, suggesting a crucial role of
galectin-9 in IFN--stimulated fibroblasts as a physiological
modulator at the inflammatory sites. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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-galactosides and share certain conserved sequence
elements (1, 2, 3, 4, 5, 6). To date, 14 galectins (galectin-1 to -14)
in mammals have been cloned and sequenced. They have been shown to play
roles in diverse biological events, including adhesion and
proliferation of cells, apoptosis, mRNA splicing, and modulation of
immune responses (1, 4, 7). However, the mechanisms by
which galectins exert these diverse effects are largely unknown. Human galectin-9 was first cloned from a cDNA library derived from tissue associated with Hodgkin’s disease. It has two CRDs connected by a linker peptide (8). Due to the difference in their linker length, there are three types of isoforms (long, medium, and short) in galectin-9 (9, 10, 11). We have independently purified and cloned a novel eosinophil chemoattractant (ECA) from T lymphocytes, and found it is identical with the galectin-9 molecule (12). Further, we have shown that galectin-9 requires divalent galactoside-binding domains to exhibit its potent ECA activity (13).
We hypothesized that galectin-9 was involved in the accumulation
of eosinophils at inflammatory sites because galectin-9 was an
eosinophil chemoattractant. In the present study we first examined the
distribution of galectin-9 in inflammatory lung disease with eosinophil
infiltration. Immunohistochemical analysis showed that galectin-9
was expressed in inflammatory cells around eosinophils, including
fibroblasts (Fig. 1
). Eosinophils play a
role in various pathological situations, including allergic
inflammation, parasitic infections, and neoplastic diseases
(14). Previous studies have shown the effects of
eosinophils on fibroblast properties. For example, human eosinophils
stimulate DNA synthesis and matrix production of dermal fibroblasts
(15, 16), and guinea pig peritoneal eosinophils enhance
the replication of fetal lung fibroblasts (17).
Several reports have examined the relation between galectins and
fibroblasts. Galectin-3 could induce the proliferation of human lung
fibroblasts (18). Galectin-1 had the ability to convert
dermal fibroblasts into the myogenic lineage (19). Taken
together, these results lead to the hypothesis that galectins,
especially galectin-9, might be involved in eosinophil-fibroblast
interaction. However, to our knowledge, no previous report has
described the regulation and functional significance of galectin-9
expression in fibroblasts, and thus in the present study we addressed
the correlation among fibroblast, galectin-9, and eosinophils.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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IFN- was purchased from Roche Molecular Biochemicals
(Mannheim, Germany). IFN- was obtained from Strathmann Biotech
(Hamburg, Germany). Basic fibroblast growth factor (FGF) was purchased
from Genzyme (Cambridge, MA). Platelet-derived growth factor AB
(PDGF-AB), IL-4, and PMA were obtained from Sigma-Aldrich (St.
Louis, MO).
Cell culture
Normal diploid human fetal fibroblasts (HFL-1; Riken Gene Bank, Ibaraki, Japan) were cultured in Ham’s F-12 medium supplemented with 15% FBS, 100 U/ml penicillin, 100 µg/ml streptomycin, and 250 ng/ml amphotericin B at 37°C in an atmosphere of 5% CO2 and 95% air.
RNA extraction, RT-PCR, and real-time PCR
To verify the expression of human galectin-9 mRNA, HFL-1 cells (1–2 x 106 cells/75 cm2) were cultured in the presence or the absence of various cytokines for 24 or 48 h. Total RNA was extracted with TRIzol (Life Technologies, Paisley, U.K.) according to the manufacturer’s instructions. RNA (0.5 µg) was reverse transcripted for 15 min at 42°C with 2.5 U of Moloney murine leukemia virus reverse transcriptase (Perkin Elmer, Norwalk, CT), using oligo(dT)16. The galectin-9 mRNA and GAPDH mRNA were detected by RT-PCR assay.
The primers 5'-GCCATCAATGACCCCTTCATTGAC-3' and 5'-ACGGAAGGCCATGCCAGTGAGCTT-3' were used to detect GAPDH mRNA expression. The expected fragment size was 609 bp.
The primers 5'-GATGAGAATGCTGTGGTCCG-3' and 5'-GAAGCCGCCTATGTCTGCA-3' were used to detect human galectin-9 mRNA expression. The expected fragment size was 260 bp.
The RT-PCR program consisted of 30 cycles with denaturation at 94°C for 30 s, annealing at 60°C for 15 s, and extension at 72°C for 1 min. Amplification was conducted using a DNA thermal cycler (Perkin Elmer).
For the quantitative real-time PCR analysis of human galectin-9 mRNA levels, a Light Cycler System and reagents (Roche Molecular Diagnostics) were used with a dsDNA binding dye, SYBR Green 1, according to the procedure provided by the manufacturer. The real-time PCR program for galectin-9 consisted of 40 cycles with denaturation at 95°C for 15 s, annealing at 69°C for 5 s, and extension at 72°C for 10 s. For GAPDH it consisted of 40 cycles with denaturation at 95°C for 15 s, annealing at 66°C for 5 s, and extension at 72°C for 20 s.
Generation and purification of a polyclonal Ab for human galectin-9
As described previously (10), anti-galectin-9 IgG was generated and purified from sera of rabbits immunized with a mixture of recombinant C-terminal CRD of human galectin-9 (galectin-9 CT) and CFA.
Immunohistochemistry
Histopathological samples obtained from a 56-year-old woman with interstitial pneumonia and from a 21-year-old woman with eosinophilic pneumonia were stained with Giemsa reagent. Distribution of galectin-9 in these samples was examined by immunohistochemical staining. Tissue sections mounted on aminopropyltriethoxy-silane-coated glass slides were deparafinized, rehydrated, and boiled by microwave irradiation in 0.01 M citrate buffer (pH 6.0) for Ag retrieval. The slides were incubated for 30 min with 0.3% hydrogen peroxide in methanol to quench endogenous tissue peroxidase activity. Immunostaining was performed using 5 µg/ml anti-galectin-9 Ab. After overnight incubation at 4°C in a moist chamber, the samples were incubated with ENVISION+ (DAKO, Glostrup, Denmark), according to manufacturer’s instructions. The immunohistochemical reactions were visualized using diaminobenzidine as a chromogenic peroxidase substrate. Sections were counterstained with hematoxylin after immunostaining.
Western blot analysis
After 24-h preincubation, HFL-1 cells were treated with IFN-
for 24 h unless otherwise specified. Lysis buffer (10 mM Tris-HCl
(pH 7.2), 0.15 M NaCl, 2 mM EDTA, 5 mM benzamidine-HCl, and 1 mM PMSF)
plus 100 mM sucrose was added to the cells. Then the mixtures were
homogenized and centrifuged. One milliliter of buffer containing 100 mM
lactose was added, and the mixture was centrifuged twice. The secondary
supernatants were used as cell lysates for electrophoresis. SDS sample
buffer was added to the cell lysates, and samples were incubated for 5
min at 95°C, then placed on ice. Samples were run on 10%
acrylamide-SDS gels and transferred to a polyvinylidene difluoride
membrane (Bio-Rad, Hercules, CA). Nonspecific binding was blocked using
5% skim milk in TBS containing 0.05% sodium azide. The membranes were
then incubated at room temperature for 1 h with 2 µg/ml of
affinity-purified rabbit anti-human galectin-9 in blocking buffer.
Membranes were washed, followed by incubation with 1% skim milk in TBS
containing HRP-conjugated anti-rabbit IgG Ab (Amersham Pharmacia
Biotech, Piscataway, NJ) at room temperature for 1 h. Finally,
membranes were incubated with ECL-HRP substrate solution included in
the ECL kit (Amersham Pharmacia Biotech), and immunoblotting was
visualized by exposing the membrane to x-ray film (Fuji, Tokyo,
Japan).
Flow cytometric analysis
To assess the surface galectin-9, cells were collected by centrifugation and washed with HBSS, followed by a 30-min incubation on ice with 50 µg/ml rabbit anti-human galectin-9. After being washed twice, the cells were incubated on ice with FITC-conjugated goat anti-rabbit Ab (Santa Cruz Biotechnology, Santa Cruz, CA) for 30 min. The amount of surface galectin-9 was analyzed using a flow cytometer (EPICS XL-MCL; Coulter, Hialeah, FL).
Eosinophil chemoattractant activity
ECA activity was evaluated in vitro as described previously (12, 20). In brief, CD16-negative eosinophils were enriched by subjecting PBL from healthy volunteers to a discontinuous density gradient of Percoll (Amersham Pharmacia Biotech), followed by immunomagnetic treatment of the cells with anti-CD16 Ig (Dako). The purity and viability of the purified eosinophils were >97 and >95%, respectively. ECA activity was evaluated using a 48-well chamber (NeuroProbe, Cabin John, MD) containing a polyvinyl pyrolidone-free membrane with a pore size of 5 µm. Human eosinophils (0.5–1 x 106/ml) and a test chemoattractant were placed in the top and bottom chambers, respectively. Each assay was performed in triplicate. The membrane separating the two chambers was removed and placed in Diff-Quick stain (Baxter Healthcare Corp., McGaw Park, IL) after 2 h of incubation at 37°C in a humidified atmosphere of 5% CO2. Stained eosinophils were counted under a microscope. Human C5a (Sigma) was used as a positive chemoattractant.
ECA activity was represented by a chemotactic index (CI = migrated eosinophil number related to the test chemoattractant/the number related to the supernatant of nonstimulated HFL-1 cells). Data represented the mean CI ± SD of experiments performed in triplicate.
Expression and purification of recombinant proteins
Recombinant proteins were obtained as described previously
(13) with minor modifications. In brief, Escherichia
coli BL-21 containing galectin-1 or galectin-9 expression plasmid
was grown in 2xYT medium supplemented with 2% (w/v) glucose and 100
µg/ml ampicillin to an OD of 0.7 at 600 nm.
Isopropyl--D-thiogalactopyranoside was added
to a final concentration 0.1 mM, and the culture was continued for
2 h at 37°C. The cells were harvested by centrifugation at
8000 x g for 10 min and resuspended in 90 ml of lysis
buffer containing 10 mM Tris-HCl, 0.5 mM sodium chloride, 1 mM DTT, and
1 mM PMSF. The cells were lysed using a sonicator, and lysates were
centrifuged at 12,000 x g for 30 min. The supernatant
was collected and applied to a lactose-agarose column (Seikagaku Corp.,
Tokyo, Japan). The adsorbed proteins were eluted using TBS containing
200 mM lactose. Fractions were collected, and proteins were analyzed by
SDS-PAGE. Fractions containing the expressed protein were pooled and
dialyzed against PBS containing 0.1 mM DTT.
Adhesion assay
HFL-1 cells grown to 
70% confluence in a 35-mm diameter dish
were stimulated with 100 U/ml IFN- for 24 h, washed with RPMI
1640 containing 5% FBS, and incubated for 2 h with human
eosinophils or neutrophils (1.0 x 105/200
µl/dish). Nonadherent cells were removed by washing twice with RPMI
1640. Adherent cells were fixed using 10% formalin, and the cells were
counted in 10 randomly selected fields (magnification, x100).
In separate experiments 2 ml of recombinant human galectin-9 (30 nM) in PBS was added to 35-mm diameter dishes and kept at 4°C for 24 h to prepare galectin-9-coated dishes. Then the recombinant protein was removed, and eosinophils or neutrophils (1.0 x 105/200 µl/dish) were cultured on these dishes at 37°C in a humidified atmosphere of 5% CO2 for 2 h. Adherent cells were counted as described above. Galectin-1-coated dishes were used as a control.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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We first examined the localization of galectin-9 in inflammatory
lung disease with tissue eosinophilia. In the interstitial pneumonia,
evident eosinophil infiltration was observed in the inflammatory sites,
and immunoreactive galectin-9 was detected in fibroblasts, vascular
endothelial cells, and inflammatory cells such as macrophages and
eosinophils themselves (Fig. 1
, A–C). In the tissue of
eosinophilic pneumonia, potent staining of immunoreactive galectin-9
was also observed in the various types of cells, including fibroblasts
and inflammatory cells around eosinophils (Fig. 1, D–F).
From these results, we considered the possibility that the expression
of galectin-9 in inflammatory cells, including fibroblasts, is directly
involved in eosinophil infiltration. Therefore, additional experiments
were performed to clarify the relationship among galectin-9,
fibroblasts, and eosinophils.
IFN- up-regulates the expression of galectin-9 in fibroblasts
Based on the immunohistochemical analysis data, we conducted the
experiment to clarify whether various fibroblast-affecting cytokines,
including IFN-, IFN-, basic FGF, PDGF-AB, and PMA, induce
galectin-9 mRNA expression in HFL-1 cells. Among them, only IFN-
up-regulated the expression of galectin-9 mRNA, while all other
cytokines did not up-regulate it (data not shown).
The results of RT-PCR and real-time PCR analyses are shown in Fig. 2. HFL-1 cells did not express galectin-9
under resting conditions. IFN-, however, up-regulated the expression
of galectin-9 mRNA (Fig. 2A). Such up-regulation of
galectin-9 mRNA was detected by IFN- stimulation at concentrations
of >3 U/ml. The results of the quantitative real-time PCR analysis
were almost identical to those of conventional RT-PCR (Fig. 2B).
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were assessed
using RT-PCR (Fig. 2C) and real-time PCR analyses (Fig. 2D). Galectin-9 mRNA became evident 6 h after
stimulation with 100 U/ml IFN-, reached its maximum at 24 h,
and decreased thereafter.
We also tested the effect of IL-4, known as a Th2 cytokine, on
galectin-9 mRNA expression in HFL-1 cells. Incubation of HFL-1 with
IL-4 (1–100 ng/ml) alone had no or little effect on galectin-9
expression, and IL-4 did not synergize with IFN- to increase
galectin-9 mRNA expression (Fig. 2E).
We further examined whether IFN- stimulation up-regulates the
galectin-9 mRNA expression in primary human dermal fibroblasts.
Galectin-9 mRNA expression in primary human dermal fibroblasts was
up-regulated by IFN- stimulation at concentration of 100 U/ml for
24 h (Fig. 2F).
Galectin-9 protein expression in fibroblasts stimulated with
IFN-
Western blot analysis of galectin-9 is shown in Fig. 3A. In accordance with the
RT-PCR results, no evident band of galectin-9 protein in HFL-1 cells
was detected without IFN- stimulation. Among three isoforms, the
medium-sized (35.9 kDa) and long-sized (39.5 kDa) galectin-9 proteins
were up-regulated by IFN- stimulation for 24 h.
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stimulation at
concentration of 100 U/ml for 24 h (Fig. 3B). In
primary human dermal fibroblasts, medium-sized galectin-9 protein was
up-regulated by IFN- stimulation, and a small amount of short-sized
(34.7 kDa), rather than long-sized, galectin-9 was induced by IFN-
stimulation.
Flow cytometric analysis was used to assess the expression of cell
surface galectin-9. Fig. 3C showed that HFL-1 cells
expressed a low level of galectin-9 protein on the surface under
resting conditions, and that the level of galectin-9 was up-regulated
by stimulation with IFN- for 24 h.
Eosinophil chemoattractant activity
Experiments were performed to assess whether the culture
supernatants from HFL-1 cells stimulated with IFN- exhibited ECA
activity. Fig. 4 shows that no ECA
activity was detected in the supernatants of IFN--stimulated HFL-1
cells. On the basis of these data, we hypothesized that the galectin-9
protein of fibroblasts exhibits biological functions other than
eosinophil chemoattraction.
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Eosinophils were added to HFL-1 cells that had or had not been
stimulated with IFN- for 24 h (Fig. 5). The numbers of eosinophils adhering
to nonstimulated and IFN--stimulated HFL-1 cells were 3.0 ±
2.2 and 25.4 ± 9.8 cells/field, respectively (mean ± SD;
p < 0.001, by Student’s t test). Both 10
and 30 mM lactose significantly reduced the number of adherent
eosinophils. Lactose (30 mM) reduced it to 4.2 ± 2.7 cells/field,
which was more effective than 10 mM lactose (10.3 ± 3.7
cells/field). In contrast, the same amount of sucrose did not reduce
the number of adherent eosinophils (10 mM, 24.7 ± 6.7
cells/field; 30 mM, 23.2 ± 8.6 cells/field). Further, 10 µg/ml
anti-galectin-9 Ab significantly reduced the number of adherent
eosinophils to 2.8 ± 2.2 cells/field. Neither anti-galectin-1
Ab (10 µg/ml) nor normal rabbit IgG (10 µg/ml), which were used as
negative controls, inhibited eosinophil adhesion to HFL-1. In contrast
to eosinophils, neutrophils did not adhere to HFL-1 cells even after
stimulation of HFL-1 cells with IFN- (adherence to nonstimulated
HFL-1 cells, 1.4 ± 1.5; that to IFN--stimulated cells,
1.6 ± 1.8). These findings suggested that galectin-9 on the
surface of HFL-1 cells preferentially mediated eosinophil adhesion to
the cells.
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showed that the numbers of eosinophils
adherent to the control and to the galectin-9-coated dish were 2.1
± 1.2 and 18.6 ± 6.6 cells/field, respectively (mean ± SD;
p < 0.001, by Student’s t test). Lactose
(30 mM) significantly reduced the number of adherent eosinophils to
4.6 ± 1.5 cells/field (p < 0.001),
whereas sucrose (30 mM) did not (16.4 ± 9.6 cells/field).
Recombinant galectin-1 was used as a control. In contrast, eosinophils
failed to adhere to the galectin-1-coated dish (Fig. 6), indicating
that galectin-9, but not galectin-1, selectively mediates eosinophil
adhesion. Further, we also confirmed that neutrophils did not adhere to
the galectin-9-coated dish (data not shown).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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exhibits diverse effects on cells of the immune system,
serving as an important regulator of lymphocyte and macrophage
functions (21, 22). IFN- also has
anti-proliferative effects on many cell types (22),
including fibroblasts (23, 24). In the present study we
demonstrate that IFN- stimulated the expression of galectin-9 in
fibroblasts. Neither basic FGF nor PDGF-AB, which are known fibroblast
stimulators, induced the expression of galectin-9 mRNA in HFL-1 cells
(data not shown). We have previously shown that stimulation of Jurkat T
cells with PMA results in the up-regulation of galectin-9 expression
(10). However, we have found that PMA does not enhance the
expression of galectin-9 mRNA in HFL-1 cells (data not shown),
indicating that the signal for galectin-9 expression differs according
to cell type, though the mechanism of regulation is still unclear.
There are three isoforms of galectin-9 that differ in the length of the
linker peptide (9, 10, 11), and all of them have comparable
ECA activities (11). In this study IFN- up-regulated
mainly the medium-sized galectin-9 in both HFL-1 and primary human
dermal fibroblasts (Fig. 3, A and B). However,
IFN- also up-regulated the long galectin-9 in HFL-1 (Fig. 3A), while the short galectin-9 was up-regulated by IFN-
in primary human dermal fibroblasts (Fig. 3B). This
different regulation of galectin-9 isoforms may reflect the functional
variance among them. Further study is required to ascertain the
mechanisms of their different up-regulation between HFL-1 and primary
human dermal fibroblasts.
Fibroblasts are involved in the pathogenesis of fibrotic diseases in
various organs. These diseases are characterized by the accumulation of
extracellular matrix collagen as a consequence of the increased
proliferation of fibroblasts. Eosinophils and fibroblasts are known to
play major roles in the pathogenesis of such fibrotic diseases. For
example, it has been shown that the infiltration of eosinophils
precedes and parallels the development of bleomycin-induced pulmonary
fibrosis (25). In patients with fibrotic lung disease, the
presence of eosinophils has been found to correlate with a worse
prognosis of the fibrotic process in the lung (26, 27).
Thus, a better understanding of the interaction between eosinophils and
fibroblasts may lead to clarification of the mechanism of fibrotic
diseases. Several studies have demonstrated that eosinophils adhered to
fibroblasts stimulated with certain cytokines, such as IL-1
,
TNF-, or PMA (17, 28), and that eosinophils stimulated
the replication of fibroblasts (17). In addition,
fibroblasts induced prolonged eosinophil survival (29, 30). In the present study the level of cell surface galectin-9
protein was up-regulated by IFN- (Fig. 3C), and we found
that eosinophils, but not neutrophils, adhered to HFL-1 cells
stimulated with IFN- (Fig. 5). The eosinophil adhesion to HFL-1
cells was inhibited by lactose, but not by sucrose, indicating that
adhesion is attributable to the galectin property. In fact, such
eosinophil adhesion was inhibited by anti-galectin-9 Ab. These
results suggest that eosinophil adhesion to HFL-1 cells was mediated by
galectin-9. Further, we found that eosinophils adhered to galectin-9,
but not to galectin-1 (Fig. 6), confirming the possibility mentioned
above that galectin-9 is preferentially involved in eosinophil
adhesion. From these findings we suggest a possible role for cell
surface galectin-9 on the fibroblasts in eosinophil recruitment. Thus,
galectin-9, expressed on fibroblastic cell surface stimulated with
IFN-, adheres to eosinophils, resulting in eosinophils staying in
tissues and allowing eosinophils to perform their effector function in
tissues for extended times. The recent study demonstrated that
galectin-9 had not only ECA activity, but also several unique effects
on eosinophils, such as eosinophil activation, superoxide production,
and the prevention of eosinophil apoptosis (31). Recently,
we reported that galectin-9 suppressed the apoptosis of eosinophils
from patients with hypereosinophilic diseases, whereas it enhanced the
apoptosis of eosinophils from healthy volunteers. In contrast,
galectin-9 accelerated Fas-induced apoptosis of both eosinophils
(32). These findings suggested that galectin-9 had
heterogeneous effects on eosinophils. Therefore, further investigation
is required to clarify whether galectin-9 on the fibroblastic cell
surface prolongs eosinophil survival by preventing the apoptosis of
eosinophils.
In human lung fibroblasts, IFN- inhibits TGF--induced signaling
and collagen deposition (33). Recently, fibroblasts have
been found to produce eotaxin, which is a potent ECA, and Th2
cytokine IL-4 stimulates eotaxin production in fibroblasts
(34, 35). IFN-, also known as a Th1 cytokine, inhibits
the expression and production of eotaxin in fibroblasts (36, 37). Further, it has been shown that IFN- reduces tissue
eosinophilia by regulating Th2 cytokines, such as IL-4 and IL-5, in
various diseases, such as airway inflammation and atopic dermatitis
(38, 39, 40, 41, 42). However, our findings imply that IFN- plays a
role in eosinophil recruitment in tissues by enhancing galectin-9
expression on the surface of fibroblasts. IL-4 did not up-regulate the
galectin-9 expression in fibroblasts, and there was no or little
synergistic effect of IFN- and IL-4 on its expression (Fig. 2E). These results contradict those in previous reports
regarding the correlation among Th1- and Th2-type cytokines and
eosinophils and may reflect the complexity of the role of eosinophil
infiltration at various inflammatory sites.
Recently, galectin-9 was reported as a urate transporter
(43) that resides in plasma membranes as a transmembrane
protein when expressed in renal epithelial cells, although galectins
were commonly described as cytoplasmic or secreted proteins. We have
found the cell surface localization of galectin-9 is required for
eosinophil adhesion to fibroblasts (Fig. 3C). Further
studies are required to ascertain whether galectin-9 on the surface of
fibroblasts also acts as a urate transporter.
In conclusion, based on the results of the present experiments it is suggested that galectin-9 expression on the surface of fibroblasts plays a role in the infiltration of eosinophils and modulates the pathogenesis of eosinophilia-related diseases.
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Acknowledgments |
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Footnotes |
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2 Abbreviations used in this paper: CRD, carbohydrate recognition domain; CI, chemotactic index; ECA, eosinophil chemoattractant; FGF, fibroblast growth factor; galectin-9 CT, C-terminal CRD of galectin-9; PDGF, platelet-derived growth factor.
Received for publication April 15, 2002. Accepted for publication September 6, 2002.
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References |
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