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*
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada;
Centre hospitalier de l’Université de Montreal, Notre-Dame Hospital, Montreal, Quebec, Canada; and
Magainin Institute of Molecular Medicine, Magainin Pharmaceuticals Inc., Plymouth, PA 19462
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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-chain mRNA in PMN RNA
preparations from asthmatic patients. Using FACS analysis, surface
expression of IL-9R was detected on PMNs freshly isolated from
asthmatics, and to a lesser extent on normal controls. In addition,
protein expression of IL-9R was also detected in peripheral blood
and bronchoalveolar lavage PMNs. Furthermore, functional studies showed
that IL-9 stimulation of PMNs results in the release of IL-8 in a
concentration-dependent manner. The anti-IL-9 neutralizing Ab
suppressed this effect, but had no effect on GM-CSF-induced IL-8
release from PMNs. Taken together, these findings suggest a novel role
for PMNs in allergic disease through the expression and activation of
the IL-9R. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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, TGF-
, and IL-1;
the growth factor GM-CSF; and the chemokines macrophage inflammatory
protein-1 and -1, IL-8, and IFN-induced protein-10
(2). As such, PMNs have the potential to produce mediators
considered to be involved in the pathogenesis of various inflammatory
diseases (1, 2, 3).
Although the role of PMNs in the pathogenesis of allergic disease
remains undefined, studies have reported evidence linking the presence
of PMNs with airway damage and dysfunction (4, 5, 6). In
particular, the number of PMNs detected in bronchoalveolar lavage (BAL)
and airway mucosa have been correlated with the degree of lung
dysfunction (7, 8, 9). Furthermore, it has recently became
apparent that PMNs express many cytokine and chemokine receptors such
as IL-4, IL-13, GM-CSF, and IL-8, as well as IgE receptors
(CD23/Fc
RII, galectin-3/Mac-2) (10, 11, 12, 13, 14, 15), indicating the
ability of these cells to respond to the stimuli considered integral to
the allergic process.
IL-9 is a Th2 cytokine first described in the mouse as a T cell and
mast cell growth factor (16, 17, 18). Recently, a role of IL-9
in asthma and allergy has been supported by the findings that it has
pleiotropic activities on cell types associated with allergic diseases
including Th2 lymphocytes, mast cells, B cells, eosinophils, and airway
epithelial cells (19, 20, 21, 22, 23, 24, 25, 26). The functions of IL-9 are
mediated by the IL-9 receptor (IL-9R), which is a member of the
hemopoietin receptor superfamily (27). The IL-9R consists
of ligand specific -chain and 
-chain that is shared with IL-2,
IL-4, IL-7, and IL-15 receptors (25). More recently, the
IL-9R locus has been genetically linked to asthma and
broncho-hyperresponsiveness in humans (28).
In view of these studies, and based on the evidence that complex
interactions between various inflammatory cells, including the Th2
subset and PMNs, may occur during the bronchial inflammation associated
with asthma, we investigated whether human PMNs express the IL-9R and
respond to this inflammatory-associated cytokine. Here, we report that
PMNs from asthmatic patients express high steady-state levels of
IL-9R mRNA and protein compared with normal subjects. Furthermore,
IL-9 stimulates PMNs to produce and release IL-8, an effect that is
significantly reduced by anti-IL-9 neutralizing Ab.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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This study was approved by the Ethics Committee of the Montreal
Chest Hospital (Montreal, Quebec). Seventeen asthmatic patients, as
defined by the American Thoracic Society, were included in this study
(29). Twenty-four nonatopic nonasthmatic controls with
negative skin tests and normal spirometry were also studied. Patients
had not received inhaled or systemic corticosteroids in the last 3 mo
and were not receiving any medications other than 2 agonists.
Subjects who had upper respiratory tract infection within the last
month were excluded from the study.
Reagents and Abs
Rabbit polyclonal affinity-purified anti-IL-9R (C18)
-chain directed to C-terminal intracellular domain-specific
FITC-conjugated goat anti-mouse IgG was obtained from Santa Cruz
Biotechnology (Santa Cruz, CA). Mouse mAb anti-IL-9R directed to
N-terminal extracellular domain, neutralizing goat anti-human IL-9,
human rGM-CSF, and rIFN- were purchased from R&D (Minneapolis, MN).
Recombinant human IL-9 was purchased from Calbiochem (La Jolla, CA).
Normal rabbit serum was obtained from Cedarlane Laboratories (Toronto,
Ontario, Canada). Biotinylated horse anti-mouse IgG was obtained
from Vector Laboratories (Burlingame, CA). Affinity-purified human IgG,
FITC-conjugated mouse (IgG1) anti-CD16, IgG1 isotype control (clone
MOPC21), FITC-conjugated mouse anti-CD16 (clone 3G8),
FITC-conjugated mouse IgG1 isotype control, and goat IgG were obtained
from Sigma (Oakville, Ontario, Canada). FITC- and biotin-conjugated
F(ab')2, swine anti-rabbit IgG, mouse
alkaline phosphatase anti-alkaline phosphatase, Fast red, and
streptavidin phosphatase alkaline were obtained from Dako (Dakopatt,
Denmark). Anti-CD16 immunomagnetic beads were obtained from Miltenyi
(Auburn, CA). FBS with low endotoxin (<25 endotoxin U/ml by
Limulus amebocyte lysate Gel Clot) was obtained from HyClone
(Logan, UT). RPMI 1640, antibiotics (penicillin, streptomycin), dNTP,
and Superscript reverse transcriptase were obtained from (Life
Technologies, Grand Island, NY). Ficoll-Paque gradients, dextran 70,
and Taq polymerase were obtained from Pharmacia Biotech
(Uppsala, Sweden). Anti-digoxigenin-alkaline phosphatase Fab, CPD-Star,
digoxigenin dideoxy-UTP, terminal transferase, and blocking reagent
were obtained from (Roche, Laval, Quebec, Canada).
Isolation and purification of human peripheral blood PMNs
PMNs were purified as previously described (30). In brief, human blood was diluted with Ca2+/Mg2+-free PBS, then overlaid onto a Ficoll-Paque gradient and centrifuged at 400 x g for 20 min. The granulocyte-rich fraction was then mixed with dextran 70, and the RBCs were allowed to sediment for 30 min at room temperature. Supernatants were collected and centrifuged for 10 min at 400 x g to recover the granulocytes, and residual RBCs were lysed with hypotonic saline. Granulocytes were then incubated with anti-CD16-coated microbeads for 30 min at 4°C in PBS/1% BSA, and washing the cells through a MACS column eluted the contaminating cells (mainly eosinophils). The differential cell count was consistently >98% PMNs as determined by staining cytospin preparations with Diff-Quick (Fisher Scientific, Ontario, Canada). The viability of the cells was >98% as determined by trypan blue exclusion.
RT-PCR and Southern blot analysis
Total cellular RNA was extracted from highly purified peripheral
blood PMNs isolated from asthmatics and normal controls, or HL-60 cell
line using TRIzol method (Life Technologies, Gaithersburg, MD). Reverse
transcription (RT) was performed by using 2 µg of total RNA in a
first-strand cDNA synthesis reaction with SuperScript reverse
transcriptase as recommended by the supplier. PCR was performed by
adding 1 µl of the RT product into 50 µl of total volume reaction
containing 1x buffer, 200 µmol of each dNTPs, 20 pmol of each
oligonucleotide primer, and 0.2 U Ampli-Taq polymerase.
Oligonucleotides specific for IL-9R sequences were used in the PCR.
Oligonucleotide primers were synthesized on the basis of the entire
coding region of the human IL-9R (GenBank accession no. M84747) as
described in Table I
. The PCR (IL-9R,
35 cycles; actin, 25 cycles) was conducted in a thermal cycler
(PTC100; MJ Research, Watertown, MA). Each cycle including denaturation
(94°C, 1 min), annealing (IL-9R-chain, 60°C (primers R7-R8) or
62°C (primers R6-R8); actin, 55°C for 2 min), and extension
72°C (90 s). The initial denaturation period was 5 min, the final
extension was 10 min. actin was amplified as an internal control.
Amplified products were analyzed by DNA gel electrophoresis in 2%
agarose, visualized by ethidium bromide staining under UV illumination
and blotted on Hybond N membrane (Amersham, Arlington Heights, IL)
using standard methods (31). Oligonucleotide probes (R6
and R18) were labeled with digoxigenin-11-dideoxy-UTP using terminal
transferase (31). The blots were prehybridized for 2
h at 42°C in hybridization solution (50% formamide, 5% SSC, 0.1%
sodium laurysarcosine, 0.1 mg/ml poly(A), 0.02% SDS, and 2% blocking
reagent). Hybridization was performed with digoxigenin-labeled
oligonucleotide probe for 18 h at 42°C. The blots were washed at
high stringency conditions: three times at room temperature in 2x SSC,
0.05% SDS and twice at 60°C in 0.1x SSC, 0.05% SDS for 30 min
each. The blots were equilibrated in washing buffer (100 mM maleic
acid, 150 mM NaCl; pH 7.5; 0.3% v/v Tween 20) for 5 min, then
incubated goat-anti digoxigenin-alkaline phosphatase Fab (1:20,000) in
blocking solution for 30 min, washed twice with washing buffer at room
temperature for 15 min each. After equilibration with detection buffer
(100 mM Tris-HCl, 100 MM NaCl; pH 9.5) for two min, the blots were
incubated for 5 min with CPD-Star diluted in detection buffer (1:100).
For detection of chemiluminescent signal, the blots were exposed to
x-ray film for 20 min at room temperature.
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Samples of 105 PMN in 100 µl of 1x
PBS/5% FBS were incubated for 30 min on ice with the primary Abs (mAb
anti-IL-9R (5 µg/ml) or IgG1 control) in the presence of 1 mg/ml
of human IgG Ig to block nonspecific binding. The cells were washed
twice with PBS/2%FBS and incubated with FITC-conjugated goat
anti-mouse IgG (1:200) in the dark for 30 min on ice. The cells
were washed again with PBS/2%FBS, resuspended in 0.3 ml of PBS, and
analyzed on FACScan. PMNs preparations were analyzed for the expression
of FcRIII using fluorescein-conjugated CD16 mAb (IgG1, dilution
1:20) or isotype-matched control used at the same concentration. The
results are presented as percentage of positive cells using CellQuest
software (Becton Dickinson, Mountain View, CA).
Cytospin preparations
Cytospin slides were prepared from BAL or peripheral blood PMNs, fixed in 4% paraformaldehyde for 20 min at room temperature, and washed with 0.05 M Tris-HCl-buffered isotonic saline, pH.7.6 (TBS). After drying, the slides were stored at -20°C before immunocytochemistry.
Single immunohistochemistry
The cytopreparations of purified blood PMNs were washed with
TBS, and saturated for 30 min with TBS/10% of human normal serum/5%
of normal goat serum. Cells were incubated with monoclonal
anti-IL-9R or isotype-matched control each at 5 µg/ml
overnight at 4°C. After washing, rabbit anti-mouse Ig (1:60) was
added for 30 min at room temperature followed by alkaline phosphatase
anti-alkaline phosphatase (1:60) for 30 min at room temperature. After
wash with TBS, the slides were developed using Fast red and
counterstained with Mayer’s hematoxylin.
The cytopreparations of BAL cells were washed with TBS and saturated
for 30 min with TBS/10% human normal serum/5% normal goat serum.
Cells were incubated with affinity-purified rabbit polyclonal
anti-IL-9R (1 µg/ml) or normal rabbit serum (1:500) overnight
at 4°C. After washing, biotinylated swine anti-rabbit (1:200) was
added for 30 min at 37°C followed by streptravidin-conjugated
alkaline phosphatase (1:200) for 1 h at room temperature. After
wash with TBS, the slides were developed using Fast red and
counterstained with Mayer’s hematoxylin (Surgipath Canada, Manitoba,
Canada).
Double immunohistochemistry
BAL was performed as described previously (32). BAL
slides were first hydrated with TBS for 5 min at room temperature
followed by a blocking step with TBS/10% human normal serum/5% normal
goat serum for 30 min at room temperature. After washing for 5 min with
TBS, polyclonal anti-IL-9R (1 µg/ml) and anti-neutrophil
elastase mAb (1:100) in TBS/10% human normal serum were applied for
2 h at room temperature. Then preparations were washed with TBS
three times for 5 min each and incubated with biotinylated horse
anti-mouse IgG (1:100) in TBS/10% human normal serum for 1 h
at room temperature. The cytopreparations were incubated with FITC
conjugated (F(ab')2 swine anti-rabbit (1:200)
and streptavidin-conjugated alkaline phosphatase (1:200) for 45 min at
37°C in dark. After the revelation step with Fast red, slides were
washed and counterstained with Mayer’s hematoxylin.
Cell line and culture conditions
The human cell line HL-60 was provided from American Type Culture Collection (Manassas, VA). Cells were cultured at 37°C in humidified 5% CO2 in RPMI 1640 medium supplemented with 10% heat-inactivated FBS and antibiotics (100 U/ml penicillin and 100 µg/ml streptomycin). Differentiation toward neutrophils was performed as described previously (33). Briefly, cells were grown in RPMI 1640, 10% FBS in the presence of DMSO (1.25%V/V) for 7 days to generate neutrophils.
PMNs stimulation and IL-8 quantification
Freshly isolated PMNs from asthmatics (2 x
106/ml) were incubated at 37°C in humidified
5% CO2 in RPMI 1640 medium supplemented with
10% heat-inactivated FBS and antibiotics for 18 h in the presence
of graded concentration of human rIL-9 (0.1, 1, and 10 ng/ml) or medium
alone. PMNs stimulated with rIFN- or rGM-CSF both at 10 ng/ml was
performed under the same culture condition. The concentration of
neutralizing goat polyclonal anti-IL-9 was chosen from preliminary
concentration-response experiments. PMNs were preincubated for 1 h
with either goat polyclonal anti-IL-9 or goat IgG both at 1 µg/ml
in complete RPMI 1640 at 37°C in humidified 5%
CO2. Cells were then stimulated or not with
either rIL-9 or rGM-CSF both at 10 ng/ml. After culture, supernatants
were removed, clarified by centrifugation, and stored at -80°C until
analysis. Immunoreactive IL-8 within the supernatants was quantitated
using an ELISA kit obtained from R&D Systems (Minneapolis, MN)
according to the manufacturer’s protocol. The sensitivity limit of
these kits is 10 pg/ml.
Statistics
Data are presented as mean ± SD. Statistical significance was determined using a Mann Whitney U test and paired Student’s t test. Values of p < 0.05 were considered statistically significant. Statistical analyses were performed with the use of a standard computer package (Systat version 7.0; Systat, Evanston, IL).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Previous studies have shown that IL-9R is expressed in many
hemopoietic cells associated with allergic diseases including T cells,
mast cells, and macrophages (34). In this study, we first
determine whether freshly isolated peripheral blood PMNs express
steady-state IL-9R mRNA levels. RNA preparation from highly purified
PMNs was first analyzed by RT-PCR. As shown in Fig. 1B, mRNA of IL-9R was
detected in all RNA preparations from asthmatic patients
(lanes 1–7) and also in three of seven PMN RNA
preparations purified from normal controls (lane
8–14). The presence of IL-9R mRNA in human PMNs from
asthmatics and normal controls was confirmed using RT-PCR with other
IL-9R-specific primers (Fig. 1C). Furthermore,
IL-9R-chain was detected in PBMCs used as positive control but not
in undifferentiated HL-60 cell line (negative cell line), respectively
(Fig. 1, B and C, lanes 15 and
16). actin-specific amplification products were of
similar intensity between all samples suggesting equality of the RNA
preparations (Fig. 1D).
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in human PMNs
To investigate whether the IL-9R is expressed on the cell
surface of human PMNs, purified cells from separate donors were
analyzed by cytofluorography using a mouse anti-IL-9R mAb.
Analysis of these samples showed that the IL-9R-chain was detected
on the surface of PMNs from asthmatic and to lesser extent in normal
controls. As shown in Fig. 2, A and B, CD16-positive PMNs from two asthmatics
expressed on their surface the IL-9R-chain with mean percentage of
positivity 88 and 49%, respectively. Cell surface IL-9R expression was
subsequently confirmed in additional asthmatics. In every case, the
IL-9R-chain expression was readily detectable with mean percentage
of positive cells of 44.7 ± 6.6% (n = 17, Fig. 3). In addition, although the majority of
PMNs from >50% of normal did not showed IL-9R surface expression
(n = 10 of 18) (Figs. 2D and 3), PMNs from
eight normal controls showed IL- IL-9R surface expression (Fig. 2C) with a mean positivity of 22.1 ± 11.6%
(n = 8). Comparison between both groups showed a
statistical difference (p < 0.001, Fig. 3).
Taken together, these results demonstrated that human PMNs express the
IL-9R with high level in asthmatics compared with controls.
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protein in peripheral blood and BAL PMNs by
immunohistochemistry
To further investigate the protein expression of the IL-9R by
human PMNs, immunocytochemistry was first performed with monoclonal
anti-IL-9R Ab on human peripheral blood PMNs. A specific
staining within the cytoplasm and the membrane was observed in PMNs
from an asthmatic donor (Fig. 4A). In contrast, PMNs in some
normal controls showed a specific staining either within the cytoplasm
or on the surface (arrows in Fig. 4, C and E).
Substitution of the first Ab with an isotype control eliminated the
immunostaining of the positive cells, demonstrating the specificity of
the analysis (Fig. 4, B, D, and
F).
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protein levels within the
cytoplasm of peripheral blood PMNs isolated from asthmatics and normal
controls. Interestingly, while IL-9R was expressed in the cytoplasm
of PMNs from all asthmatic donors with a variable level, little or no
expression was observed in the majority of PMNs from normal controls
(n = 11 of 18), and there was a significant difference
in the level of IL-9R expression in PMNs between asthmatics and
normal controls (p = 0.001, Fig. 5).
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in BAL cells from
asthmatics. Positive immunoreactivity for the polyclonal IL-9R-chain
Ab is observed in a subset of BAL cells exhibiting PMNs morphology
(Fig. 4
G). Similar result was observed with monoclonal
anti-IL-9R Ab (data not shown).
To determine whether positive cells were PMNs, we performed double
immunocytochemistry using mouse anti-elastase mAb, as marker of
PMNs, and the polyclonal anti-IL-9R-chain Ab. Here we show the
coexpression of IL-9R-chain and the elastase within the same cell
(Fig. 4, I and K, respectively). However, no
staining was observed on BAL cells with the isotype-matched Abs (Fig. 4, J and L). Furthermore, a positive
immunostaining was also detected in PMNs within the airways of
asthmatic patients (data not shown). This result confirmed that PMNs
express the IL-9R-chain.
IL-9 and IL-9R mediated IL-8 release from human PMNs
To verify that the IL-9R expressed in human PMNs was functional,
we examined whether stimulating human PMNs with IL-9 could induce the
release of IL-8, because IL-8 production is a common feature in
inflammation process (35). Peripheral blood PMNs from
asthmatics were stimulated with or without rIL-9 and evaluated for IL-8
release in culture medium after 18 h. As shown in Fig. 6, rIL-9 induced the synthesis and
release of IL-8 in a dose-dependent manner. The minimal effective dose
of rIL-9 was 1 ng/ml (Fig. 6A). Indeed, the levels of IL-8
released in the external milieu of rIL-9-stimulated PMNs was almost
5-fold increased when compared with control cells (192 ± 40 pg/ml
vs 35 ± 18 pg/ml, respectively, p < 0.01,
n = 4), and high levels of IL-8 were detected in
rGM-CSF-stimulated PMNs (1117 ± 115 pg/ml, n = 4,
Fig. 6B). However, a slight decrease of IL-8 release was
observed when the same preparations of PMNs were incubated with
rIFN- (27 ± 16 pg/ml, Fig. 6B)
(36).
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A), but had no effect on
rGM-CSF-induced IL-8 (Fig. 7B). In contrast, goat IgG had no
significant effect on IL-8 release from PMNs incubated with rIL-9,
rGM-CSF, or medium (Fig. 7, A and B).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In this study, we investigated the expression of the IL-9R as well as
the ability of IL-9 to induce functional activation of human PMNs. The
expression of the IL-9R was established by FACS,
immunohistochemistry, and RT-PCR analysis of freshly isolated human
peripheral blood PMNs. Furthermore, IL-9R expression was also detected
in BAL-derived PMNs from asthmatic patients. These data demonstrate
that PMNs express the IL-9 cell surface receptor. We also showed that
IL-9 can induce the production and the release of IL-8 by human PMNs,
an effect that was blocked by anti-IL-9 neutralizing Ab. Because
IL-8 has been reported to have chemotactic activity for various
inflammatory cells involved in allergic diseases (35),
this result provides a possible mechanism by which PMNs may contribute
to the amplification of the inflammatory response. Recently, Dong et
al. have reported that IL-9 also has direct activity on airway
epithelial cells to produce C-C chemokines such as eotaxin
(26). Together these data suggest an orchestrated activity
by which IL-9 may induce chemokines in the airway, which result in a
robust infiltration of inflammatory cells.
The recruitment of leukocytes to inflammatory sites is mediated by the
production of a number of chemoattractant mediators (37).
More recently, IL-9 has been shown to induce massive airway
inflammation in vivo (23, 24). Our results show that in
asthmatics IL-9 increased the release and production of IL-8 by PMNs in
a dose-dependent manner. Furthermore, the anti-IL-9 Ab suppressed
the effect of IL-9 on IL-8 release on PMNs but had no effect on
GM-CSF-induced IL-8. This action of IL-9 is not limited to PMNs,
because previously it has been suggested to induce chemokines
expression on epithelial cells (26). While the
intracellular mechanism underlying this effect on human PMNs has not
been investigated, the signal transduction pathway triggered by
IL-9R involves STAT1, STAT3, STAT5, and phosphatidylinositol
3-kinase (38). Whether these transcription factors are
activated following stimulation of the IL-9R in PMNs from asthmatics
remains to be determined.
The expression of the IL-9R protein on human PMNs was widely
heterogeneous according to individual donors, and there was a
significant difference between the percentage of IL-9R-positive PMNs
in asthmatics compared with normal controls analyzed by FACS and
immunohistochemistry analysis (p < 0.02). This
suggests that the expression of IL-9R is under regulatory control. A
number of potential explanations for this are under investigation. Th2
cytokines highly expressed in allergic diseases may up-regulate the
IL-9R expression on PMNs from asthmatics. This is in line with
previous report indicating that the Th-2 cytokines, in particular
GM-CSF and IL-4, exert several actions on PMNs, including stimulation
or changes in expression of many surface receptors (8, 10, 11, 39). Further support for this possibility comes from studies
showing that both IL-4 and GM-CSF up-regulate the expression of
IL-9R in PMNs (S. G. Abdelilah, unpublished observation).
Although >50% of PMNs from normal controls do not express the
IL-9R as described recently (40), an interesting
feature of our study was that PMNs from some normal controls have an
intracellular store but no surface expression. This suggests that in
this particular subpopulation of PMNs the IL-9R protein may be
associated with a yet to be defined structure(s) that precludes its
surface expression. Furthermore, the -chain is shared by IL-2, IL-4,
and IL-15 receptors (25), which have been shown to be
expressed on the surface of human PMNs (11, 41, 42). One
can speculate that the surface expression of those cytokine receptors
may have a negative regulatory effect on IL-9R surface expression by
competing for -chain during IL-9R assembly. This situation was
recently reported for FcRI in mast cells (43). In
contrast, the coupling mechanisms leading to active association of
IL-9R subunits are deficient or are themselves subject to distinct
regulatory signals in PMNs from some normal controls. Furthermore, PMNs
from some normal controls showed IL-9R surface expression that
suggest that this population of PMNs are stimulated in vivo by factors
other than Th-2 cytokines. Further studies are in progress to clarify
these and other possible mechanism with regard to the regulation of
IL-9R in PMNs.
In the context of local allergic inflammation, the release of IL-8 by human PMNs after IL-9 stimulation may be involved in the recruitment of inflammatory cells (23, 24, 34). In line with these suggestions, IL-8 has been previously shown to be a chemotactic factor for activated T lymphocytes, eosinophils, and basophils and to enhance the expression of integrins on monocytes as well as their adherence to endothelial cells (35). Collectively, the results of this study provide a novel mechanism by which PMNs may contribute to the inflammatory reaction via an IL-9-dependent mechanism.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Soussi Gounni Abdelilah, Meakins-Christie Laboratories, McGill University, 3626 St. Urban Street, H2X2P2, Montreal, Quebec, Canada.
3 Abbreviations used in this manuscript: PMNs, polymorphonuclear neutrophils; BAL, bronchoalveolar lavage; RT, reverse transcription.
Received for publication November 30, 1999. Accepted for publication December 5, 2000.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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BP) of the S-type lectin family: role in IgE-dependent activation. J. Exp. Med. 177:243.RII/CD23 expression on normal human polymophonuclear neutrophils. Int. Immunol. 4:479.
inhibits interleukin-8 production by human polymorphonuclear leukocytes. Immunology 78:177.[Medline]
chain (IL-15R) but not the IL-9R component. Clin. Immunol. 88:232.
RI chain results in upregulation of FcRIII-dependent mast cell degranulation and anaphylaxis: evidence of competition between FcRI and FcRIII for limiting amounts of FcR and chains. J. Clin. Invest. 99:915.[Medline]
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