| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Glucan Receptor, Dectin-1, Is Predominantly Expressed on the Surface of Cells of the Monocyte/Macrophage and Neutrophil Lineages1
* Sir William Dunn School of Pathology, Oxford University, Oxford, United Kingdom; and
The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
GR) as a major -glucan
receptor on leukocytes and demonstrated that it played a significant
role in the non-opsonic recognition of soluble and particulate
-glucans. Using a novel mAb (2A11) raised against GR, we show
here that the receptor is not dendritic cell-restricted as first
reported, but is broadly expressed, with highest surface expression on
populations of myeloid cells (monocyte/macrophage (M
) and neutrophil
lineages). Dendritic cells and a subpopulation of T cells also
expressed the GR, but at lower levels. Alveolar M, like
inflammatory M, exhibited the highest surface expression of GR,
indicative of a role for this receptor in immune surveillance. In
contrast, resident peritoneal M expressed much lower levels of GR
on the cell surface. Characterization of the nonopsonic recognition of
zymosan by resident peritoneal M suggested the existence of an
additional -glucan-independent mechanism of zymosan binding that was
not observed on elicited or bone marrow-derived M. Although this
recognition could be inhibited by mannan, we were able to exclude
involvement of the M mannose receptor and complement receptor 3 in
this process. These observations imply the existence of an additional
mannan-dependent receptor involved in the recognition of zymosan by
resident peritoneal M. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-glucan receptors were first described
nearly 20 yr ago as opsonin-independent receptors for particulate
activators of the alternative complement activation pathway
(1, 2). These receptors are thought to mediate the potent
biological effects of -1,3-D-glucans, including
anti-tumor and anti-infective properties (3, 4, 5, 6, 7).
Receptors for these fungal-derived polymers have been reported on cells
of the monocyte (Mo)4/macrophage
(M)-lineage (including microglia), neutrophils, NK cells, and
fibroblasts (8, 9). To date four -glucan receptors have
been identified as candidates mediating these activities, namely
complement receptor 3 (CR3; CD11b/CD18) (10, 11),
lactosylceramide (12), selected scavenger receptors
(13), and dectin-1 (GR) (14).
We identified dectin-1 (GR) as a -glucan receptor after screening
a retroviral cDNA library derived from the M cell line RAW264.7 with
the -glucan-rich particle zymosan (14). GR consists
of a single C-type, lectin-like, carbohydrate recognition domain, a
short stalk, and a cytoplasmic tail possessing an immunoreceptor
tyrosine-based activation motif (15). The receptor
recognized particles such as zymosan, Saccharomyces
cerevisiae, and heat-killed Candida albicans in a
-glucan-dependent manner (14). The receptor could also
bind to T cells, promoting cellular proliferation in the presence of
suboptimal concentrations of anti-CD3 (15). T cell
recognition was -glucan independent, indicating the presence of a
second binding site on this receptor (14). The human
homologue of GR has also been cloned (16, 17, 18, 19) and was
found to exhibit similar properties (18).
We recently assessed the role of GR in the recognition of soluble
and particulate (zymosan) -glucans by macrophages (20).
Using a novel anti-GR mAb (2A11) that has the ability to block
the -glucan binding activity of the receptor, we found that GR
was a major receptor on M for the nonopsonic recognition of these
carbohydrates, defining GR as the missing leukocyte -glucan
receptor. Furthermore, we demonstrated that CR3 played no obvious role
in this process (20), in contrast to previous reports
(10, 21). GR was initially considered dendritic cell
(DC) restricted (15), a finding not consistent with the
distribution ascribed to the leukocyte -glucan receptor activity.
However, we isolated GR from a mouse M cell line and observed
GR transcript in murine and human M and peripheral blood
neutrophils (14, 18, 20). Given the potential importance
of the leukocyte -glucan receptor in innate immunity, we sought to
clarify the expression pattern of GR and performed a comprehensive
analysis of the distribution of this receptor in mice. We show, using
mAb 2A11, that GR is predominantly expressed on cells of the
Mo/M and neutrophil lineages, but also on DC,
as previously noted. Furthermore, a subset of splenic T cells that
expressed the Gr-1 Ag also expressed GR, albeit at low levels.
Examination of GR expression on various freshly isolated primary
M showed that alveolar and peritoneal inflammatory M expressed
high levels of the receptor, whereas resident peritoneal cells
expressed relatively low levels. As GR is responsible for the
nonopsonic recognition of zymosan by other M populations
(20), we studied zymosan recognition by the low
GR-expressing resident peritoneal cells. While GR was responsible
for -glucan-dependent zymosan recognition by these cells, a second
-glucan-independent, mannan-inhibitable, nonopsonic recognition
mechanism was also present.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
For RT-PCR analysis, total RNA from various cell lines
(RAW264.7, J774, P388D1, and NIH-3T3) and primary cell types (BMDM
and BMDDC) was prepared using the guanidine isothiocyanate-based RNA
isolation kit (Stratagene, La Jolla, CA). First-strand cDNA synthesis
was performed using the Advantage RT-for-PCR kit with an oligo(dT)
primer (Clontech, Palo Alto, CA), as described by the manufacturer. The
GR transcript was subsequently amplified using primers corresponding
to the region of the cDNA encoding residues 66–244 of the primary
protein sequence. Dihydrofolate reductase-specific primers (Stratagene)
were used as a positive control. Commercially available membranes
containing poly(A) mRNA isolated from various mouse tissues were
purchased from Origene Technologies (Rockville, MD) and were
probed as described by the manufacturer using a full-length GR cDNA
probe.
Tissue and cell preparation
All mice used in this study were C57BL/6J, unless otherwise stated, and were between 8 and 12 wk of age. Animals were kept and handled in accordance with institutional guidelines. Splenocytes were harvested by standard methods using a combination of digestion with Liberase Blendzyme II in RPMI (Roche, Indianapolis, IN) and mechanical dissociation. Femurs were collected, and fresh bone marrow was flushed from within using Liberase Blendzyme II and incubated for 10 min at 37°C to disaggregate cells. Enzymatic activity was quenched with RPMI/20% FCS, erythrocytes were lysed with Gey’s solution, and cell debris was removed by centrifugation through 100% FCS at 300 x g.
Isolation of peripheral blood leukocytes
Mice were sacrificed, and peripheral blood was collected by cardiac puncture into 0.1 vol 100 mM EDTA. Cells were harvested by centrifugation and resuspended in 50 vol Gey’s solution to lyse erythrocytes. Peripheral blood leukocytes were then recovered by centrifugation through FCS as described above.
Isolation of alveolar M
Bronchoalveolar lavage was performed by repeated washes with 1
ml PBS/5 mM EDTA. Resident alveolar M, the major leukocyte
population in the lungs, were identified by size and autofluorescence
using flow cytometry as previously described (22).
Induction of sterile peritonitis and recovery of peritoneal cells
To induce sterile peritonitis, mice were injected i.p. with 4%
thioglycolate (BD Biosciences, Franklin Lakes, NJ) up to 4 days before
peritoneal lavage. After humane killing of the animals, inflammatory
cells were collected by peritoneal lavage with ice-cold 5 mM EDTA in
PBS. Resident peritoneal cells were collected in the same way from
untreated animals. Peritoneal M were identified by their expression
of F4/80 and CR3 and were distinguished from eosinophils by forward
scatter (FSC)/side scatter (SSC) profiles. To confirm the cellular
composition of peritoneal exudates, differential counts were performed
on cytospin preparations stained with Hema Gurr (VWR International,
Poole, U.K.).
FACS analysis
FACS was performed according to conventional protocols at 4°C
in the presence of 2 mM NaN3. Cells were blocked
with 5% heat-inactivated rabbit serum, 0.5% BSA, 5 mM EDTA, and 4
µg/ml 2.4G2 (anti-Fc
RII and -III) before the addition of
primary Abs. Biotinylated Abs were detected using
streptavidin-allophycocyanin (BD PharMingen). Cells were fixed with 1%
formaldehyde in PBS before analysis.
The following Abs were used in this study: B220-CyChrome (RA3-6B2; BD
PharMingen), CD3-CyChrome (17A2; BD PharMingen), F4/80-PE (Serotec),
CD11c-PE (HL3; BD PharMingen), Gr-1-PE (anti-Ly6C/G; BD
PharMingen), CD49b-PE (DX5-Pan NK-cell; BD PharMingen), 5C6-FITC
(anti-CR3/CD11b) (23), 2A11-biotin (rat IgG2b
anti-GR) (20), 5D3-biotin (rat IgG2a anti-M
mannose receptor (MR)) (L. Martinez-Pomares, D. M. Reid, G. D.
Brown, P. R. Taylor, R. Stillion, S. A. Linehan, S. Gordon,
and S. Y. C. Wong, unpublished observations), and irrelevant rat
IgG2b-biotin, IgG2a-biotin, and IgG2b-FITC control Abs.
In vitro non-opsonic zymosan binding assay
In vitro zymosan binding assays were performed as previously
described (14, 18, 20). In brief, resident or 4-day
thioglycolate-elicited peritoneal M were recovered, as described
above, and plated at 5 x 105 and 2.5
x 105 cells/well, respectively, in 24-well
plates in RPMI/10% FCS overnight. The following day the cells were
cooled to 4°C and washed three times with prechilled medium. All
experiments were performed at 4°C to prevent receptor
internalization, to provide a direct measure of surface receptor
involvement, and to prevent local release of opsonins, including
complement (24, 25). Zymosan-FITC (Molecular Probes) was
added to the M at a ratio of 25 particles/cell for 1 h on ice.
For in vitro blocking assays, carbohydrates (laminarin,
-methylglucoside, and mannan; all from Sigma (St. Louis, MO) and
used at 100 µg/ml) or Abs (2A11 (20); 5C6
(23), which has been shown to block the CR3-mediated
lectin activity (26); or an irrelevant rat IgG2b control;
all used at 100 µg/ml) were added to the chilled cells 20 and 60 min,
respectively, before the addition of zymosan. After incubation, unbound
zymosan was removed by extensive washing with medium, and cells were
lysed with 3% Triton X-100. FITC in lysates was quantified using a
Titer-Tek Fluoroskan II (Labsystems Group, Basingstoke, U.K.) as
previously described (14, 18). For Ab modulation
experiments poly-D-lysine-conditioned tissue culture plates
were coated with Ab at 100 µg/ml as previously described
(27). All experiments were repeated at least three
times.
Statistical analysis
Statistics were calculated using GraphPad PRISM (version 2.0; GraphPad Software, Berkeley, CA). One-way ANOVA with Bonferroni multiple comparison test was applied throughout.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
GR mRNA in macrophages and multiple mouse tissues
We studied the expression of GR by RT-PCR in several M cell
lines and in primary M and DCs. All M cell lines as well as bone
marrow-derived M and DC showed evidence of GR expression, whereas
GR transcript was not detectable in the mouse fibroblast cell line
NIH-3T3 (Fig. 1
A). Using the
full-length coding sequence to screen a multiple tissue Northern blot,
we found GR expression in most murine tissues with the exception of
brain, muscle, and skin (Fig. 1B). Notably there was only
one discernible transcript detectable in these tissues.
|
GR surface expression in the spleen
We examined the surface expression of GR using 2A11 on freshly
isolated splenocytes (Fig. 2).
CD11chigh DC were found to express GR
(population 1) in a similar pattern to that reported previously
(15). Notably, however, other
CD11clow/- cells in the spleen, particularly
those expressing CR3, exhibited high surface expression of GR
(population 2). To further delineate which cell types were expressing
GR, the cells were subdivided into six populations based on their
expression of CR3 and Gr-1 (an mAb recognizing Ly-6G and Ly-6C) and
their FSC/SSC profiles (Fig. 2B).
Gr-1highCR3highSSChigh
neutrophils (population 3) exhibited high surface expression of GR,
as did Gr-1lowCR3+SSClowM
(population 4B), which also expressed F4/80 (data not shown). A second,
unidentified, population of
Gr-1lowCR3+ splenocytes
with very high SSC (population 4A) did not show evidence of GR
surface expression.
CR3+Gr-1- splenocytes, a
mixed population containing DC (CD11chigh), NK
cells, and other M (both CD11cint), showed
heterogeneity in expression of GR (population 5). NK cells, which
have been shown to recognize -glucans (8) and are
identified by high expression of the DX5 Ag (CD49b) (28),
did not show significant labeling with the 2A11 Ab (data not shown).
Gr-1lowCR3- splenocytes
(population 6), previously reported to be a T cell subset
(29), expressed CD3 and low levels of surface GR (Fig. 2C). Analysis of all splenic T cells
(CD3+) and B cells
(B220+) for GR surface expression, however,
indicated that only a distinct subset of T cells exhibited significant
surface expression of GR (Fig. 2C).
GR+CD3+T cells were
predominantly Gr-1+ and
CD8+, but CD4+ cells were
also observed (data not shown). Splenic autofluorescent
F4/80+ M also expressed GR, but at very low
levels (data not shown). Plasmacytoid DC in the spleen, which were
identified by their
Gr-1+B220+CD11cintCR3-
phenotype and analyzed in 129/SvEv and BALB/c mice because of the
relative scarcity of these cells in C57BL/6 (30), also
exhibited low, but detectable, levels of GR expression (data not
shown).
|
GR on peripheral blood leukocytes
We and others have observed expression of GR/dectin-1 on
both human and mouse PBL by Northern blot (17, 18). We
confirmed these observations by FACS by identifying a significant
population of PBL that expressed GR (data not shown). Consistent
with the data obtained from the spleen, peripheral blood neutrophils
(identified as
Gr-1highSSChigh) and
peripheral blood Mo (identified as
CR3+F4/80+SSClow)
exhibited high surface expression of GR (Fig. 3A).
|
GR on myeloid cells in the bone
marrow
Since we have previously observed the GR transcript in human
bone marrow (18), we examined murine bone marrow for the
expression of GR (Fig. 3
B).
Gr-1highCR3+ neutrophils
were subdivided into two populations. Approximately one-third of the
bone marrow Gr-1high neutrophils had high GR
surface expression; the remaining two-thirds showed intermediate or
marginal expression (populations 1 and 2, respectively; Fig. 3B). The GRhigh neutrophils had
higher SSC and higher CR3 surface expression than the
GRlow neutrophils (data not shown), suggesting
that the GRhigh neutrophils may be in a more
advanced state of maturation. This is consistent with the high GR
surface expression detected on circulating peripheral blood neutrophils
(Fig. 3A). The Gr-1low subgroup of
bone marrow cells that has been reported to include cells of the
Mo/M lineage, myeloid precursors, and
hemopoietic stem cells (31) contained cells with the
highest GR surface expression (population 3). The expression of CR3
and F4/80 indicated that these high GR-expressing cells most likely
belonged to the Mo/M lineage (data not shown).
Additional unidentified Gr-1low and
Gr-1- bone marrow cells also showed evidence of
GR expression, but these were not characterized further (Fig. 3B).
Expression of GR by isolated primary M
Freshly isolated resident and thioglycolate-elicited peritoneal
M were assayed for surface expression of GR. We also looked for
GR expression on alveolar M, as we had found a high level of
transcript in the lung (Fig. 1). Both freshly isolated alveolar M
and thioglycolate-elicited M expressed high surface levels of GR,
whereas resident peritoneal M exhibited lower expression (Fig. 4). Interestingly, we observed an
up-regulation of GR on the surface of resident peritoneal M after
1 day of culture (Fig. 4). Surface expression of GR on
thioglycolate-elicited M was relatively unaffected by 1 day of
culture (data not shown). Since the M MR is also a candidate
receptor for the nonopsonic recognition of zymosan by resident
peritoneal M (see below), we analyzed the surface expression of this
receptor on the same cells. Similar to GR, we found the highest
surface expression of the MR on thioglycolate-elicited M, moderate
expression on resident alveolar M, but only very limited expression
on the surface of resident peritoneal cells (Fig. 4). Unlike GR,
however, the expression of MR on resident peritoneal cells was
relatively unaffected by 1 day of culture (Fig. 4). As reported
previously, we found that alveolar M expressed negligible CR3
(22) (Fig. 4) and low levels of F4/80 (data not
shown).
|
GR during peritoneal inflammation
To study the expression of GR in an inflammatory context, we
examined peritoneal exudate cells 18 h after the i.p.
administration of thioglycolate, a model of sterile peritonitis.
F4/80+CR3highGr-1-
M,
F4/80-CR3+Gr-1+
neutrophils, and
F4/80+CR3+Gr-1-SSChigh
eosinophils (32) were then tested for GR surface
expression (Fig. 5). Elicited peritoneal
M exhibited the highest GR expression, and significant amounts
were also present on the inflammatory neutrophils. In contrast,
recruited eosinophils showed no obvious surface expression of GR
(Fig. 5).
|
We observed that freshly isolated resident peritoneal M
had a lower level of surface GR expression than that on other M
studied (Fig. 4). As we had previously shown that GR was a major
receptor for zymosan on thioglycolate-elicited and BMDM
(20), we wanted to determine whether this was also true
for resident peritoneal M. We compared the contribution of GR on
both resident and elicited M and found that the binding of
unopsonized zymosan to elicited M was significantly inhibited by
-glucans, as previously reported (Fig. 6) (20). GR was still a
major receptor for zymosan on resident M, but it contributed less to
this process than in the thioglycolate-elicited cells. Furthermore, we
found that mannan had an inhibitory effect on the binding of zymosan to
the resident M, but not to the thioglycolate-elicited cells (Fig. 6A). The combination of -glucans and mannan did not have
an additive effect (data not shown). As with the elicited M,
methylglucoside failed to inhibit the initial binding of zymosan to
resident peritoneal M, suggesting no involvement of CR3 in this
process (data not shown). These results implied that a secondary
-glucan-independent, mannan-inhibitable, nonopsonic binding
mechanism was operational on resident M, but was not present on
other M examined.
|
(Fig. 6B). The anti-GR mAb, 2A11, blocked the nonopsonic
binding of zymosan to resident peritoneal M to the same degree as
the soluble -glucans laminarin (Fig. 6B) and glucan
phosphate (data not shown), consistent with GR being a major
-glucan receptor on M. Anti-CR3 (5C6, which blocks the lectin
activity of CR3) had no inhibitory effect (Fig. 6B)
consistent with our previous results (20). As surface
expression of M MR was low on resident peritoneal M and higher on
thioglycolate-elicited M, which do not have a mannan-inhibitable
component of zymosan binding, the MR appears not to be involved in the
nonopsonic recognition of zymosan by the M (Fig. 4)
(20). We also performed Ab modulation experiments using
specific mAb to deplete surface receptors from the upper ligand binding
surface. Only 2A11, anti-GR-coated tissue culture wells
inhibited the nonopsonic binding of zymosan; anti-M MR and
anti-CR3, did not (data not shown). |
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
GR is a principal -glucan
receptor on primary M (20). As our data (14, 18, 20) did not agree with the previously reported DC-restricted
expression of dectin-1 (15), and as the leukocyte
-glucan receptor is believed to be more broadly expressed
(8), we re-examined the distribution of dectin-1 using the
novel anti-GR mAb 2A11. While we confirmed expression of
dectin-1 by splenic DC, we discovered that a significant proportion of
CR3+ splenocytes exhibited higher surface
expression of GR. These cells were of the
Mo/M lineage and neutrophils. Furthermore, we
also found that peripheral blood Mo and
neutrophils expressed high surface levels of GR. In the bone marrow,
cells of the Mo/M lineage were also the major
surface expressers of GR, but heterogeneous expression was evident
on Gr-1high neutrophils. This heterogeneity
appeared to be related to maturation, as
GRhigh cells had higher levels of CR3 and
higher SSC. Overall, these results were consistent with the expected
distribution of the -glucan receptor (8).
Although NK cells are thought to recognize -glucans
(33), we detected no obvious surface expression on freshly
isolated splenic NK cells. We cannot exclude, however, that expression
of GR on the surface of these cells may be regulated by activation.
Surprisingly we also observed surface expression of dectin-1 on the
Gr-1+ subset of splenic T cells, although it is
not without precedent that NK-like C-type lectins can be expressed on T
cells (reviewed in Ref. 34). It is plausible that the
expression of GR, as a T cell binding receptor, on a subset of T
cells may be part of a novel mechanism for the regulation of the T cell
response by specific subsets of T cells as well as by APC.
We have postulated that GR may play a fundamental role in the
immunomodulatory effects of -glucans and the host response to fungal
pathogens (14), and so looked for expression of this
receptor on inflammatory cells. Consistent with this, in a model of
peritoneal inflammation, elicited M and neutrophils exhibited high
GR surface expression. Although freshly isolated resident peritoneal
M exhibited low 2A11 binding, the levels of the receptor were
up-regulated within 1 day of culture (Fig. 4), indicating that GR
surface expression on M can be regulated. High levels of GR were
also detected on the CR3- resident alveolar
M, highlighting the important role this receptor may play in immune
surveillance and host defense at this portal of entry, where the
availability of complement and Ig is restricted.
Our recent studies with elicited M (both thioglycolate and Bio-Gel)
and BMDM indicated that GR was a major nonopsonic receptor for
binding of the -glucan-rich particle zymosan (20). The
observation of lower GR surface expression on resident peritoneal
M compared with the other M we have studied prompted us to
determine whether GR was the major -glucan receptor on
this cell type. Although, we found that -glucan-dependent binding of
unopsonized zymosan to resident peritoneal M was mediated by GR,
these cells also exhibited a second nonopsonic,
mannan-inhibitable binding mechanism that was not found on all
other M examined (20). The surface expression pattern
of the M MR was not consistent with a role for the MR in this
process. Our observations have hence uncovered the existence of a
second -glucan-independent, nonopsonic mechanism of binding zymosan
used by resident peritoneal M (but not by other M tested) that
was inhibitable by mannan. This additional receptor could represent the
mannan-dependent yeast receptor previously observed on resident
peritoneal M (35, 36) and implicates this receptor as a
pattern recognition receptor with a potentially important role in
host defense. The presence of this receptor activity specifically on
resident peritoneal M may also explain the controversy surrounding
the contribution of a mannan-dependent receptor to yeast/zymosan
recognition (35, 36, 37). Candidate receptors that may play a
role in this process and have demonstrated mannose binding capabilities
are DC-SIGN/DC-SIGNR (38) and NKCL (39).
In summary, we have shown that the major surface expression of GR is
on cells of the Mo/M lineage and neutrophils
and to a lesser extent on splenic DC. We have also observed low surface
expression of GR on a specific subset of splenic T cells. This
analysis of the surface expression of GR has provided novel insights
into the biology of this receptor and into the recognition of
-glucans by leukocytes.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 P.R.T. and G.D.B. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Gordon D. Brown, Sir William Dunn School of Pathology, Oxford University, South Parks Road, Oxford, U.K. OX1 3RE. E-mail address: gbrown{at}molbiol.ox.ac.uk
4 Abbreviations used in this paper: Mo, monocyte(s); M, macrophage; GR, -glucan receptor/dectin-1; DC, dendritic cell; BMDDC, bone marrow-derived DC; BMDM, bone marrow-derived M; CR3, complement receptor 3; FSC, forward scatter; MR, mannose receptor; SSC, side scatter.
Received for publication May 29, 2002. Accepted for publication August 5, 2002.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-glucan-inhibitable receptors on bone marrow-derived murine macrophages. Immunol. Res. 5:129.[Medline]
-glucan in cancer. Immunopharmacology 42:61.[Medline]
-D-glucan immunobiology. Mediat. Inflamm. 6:247.
-D-glucans. Infect. Immun. 69:3933.-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). J. Immunol. 156:1235.[Abstract]
-(1–3)-glucan immunomodulator, PGG-glucan, and lactosylceramide of human leukocytes. J. Biol. Chem. 273:22014.-glucans. Nature 413:36.[Medline]
-glucan receptor and its alternatively spliced isoforms. J. Biol. Chem. 20:20.
-glucan receptor on macrophages. J. Exp. Med. 196:407.-glucan-binding lectin site of mouse CR3 (CD11b/CD18) and its function in generating a primed state of the receptor that mediates cytotoxic activation in response to iC3b-opsonized target cells. J. Immunol. 162:2281.
2 integrin, very late antigen-2). J. Immunol. 167:1141.-glucan receptors are involved in phagocytosis of unopsonized, heat-killed Saccharomyces cerevisiae by murine macrophages. J. Leukocyte Biol. 54:564.[Abstract]
-glucan receptor of murine macrophages. Exp. Cell Res. 174:481.[Medline]
This article has been cited by other articles:
|
|
 |
|
  H. Huang, G. R. Ostroff, C. K. Lee, J. P. Wang, C. A. Specht, and S. M. Levitz Distinct Patterns of Dendritic Cell Cytokine Release Stimulated by Fungal {beta}-Glucans and Toll-Like Receptor Agonists Infect. Immun., May 1, 2009; 77(5): 1774 - 1781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Balestrieri, A. Maekawa, W. Xing, M. H. Gelb, H. R. Katz, and J. P. Arm Group V Secretory Phospholipase A2 Modulates Phagosome Maturation and Regulates the Innate Immune Response against Candida albicans J. Immunol., April 15, 2009; 182(8): 4891 - 4898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Werner, A. E. Metz, D. Horn, T. R. Schoeb, M. M. Hewitt, L. M. Schwiebert, I. Faro-Trindade, G. D. Brown, and C. Steele Requisite Role for the Dectin-1 {beta}-Glucan Receptor in Pulmonary Defense against Aspergillus fumigatus J. Immunol., April 15, 2009; 182(8): 4938 - 4946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Kerrigan, K. M. Dennehy, D. Mourao-Sa, I. Faro-Trindade, J. A. Willment, P. R. Taylor, J. A. Eble, C. Reis e Sousa, and G. D. Brown CLEC-2 Is a Phagocytic Activation Receptor Expressed on Murine Peripheral Blood Neutrophils J. Immunol., April 1, 2009; 182(7): 4150 - 4157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lin, E. De Stanchina, X. K. Zhou, Y. She, D. Hoang, S. W. Cheung, B. Cassileth, and S. Cunningham-Rundles Maitake Beta-Glucan Enhances Umbilical Cord Blood Stem Cell Transplantation in the NOD/SCID Mouse Experimental Biology and Medicine, March 1, 2009; 234(3): 342 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Balloy, J.-M. Sallenave, Y. Wu, L. Touqui, J.-P. Latge, M. Si-Tahar, and M. Chignard Aspergillus fumigatus-induced Interleukin-8 Synthesis by Respiratory Epithelial Cells Is Controlled by the Phosphatidylinositol 3-Kinase, p38 MAPK, and ERK1/2 Pathways and Not by the Toll-like Receptor-MyD88 Pathway J. Biol. Chem., November 7, 2008; 283(45): 30513 - 30521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Dioszeghy, M. Rosas, B. H. Maskrey, C. Colmont, N. Topley, P. Chaitidis, H. Kuhn, S. A. Jones, P. R. Taylor, and V. B. O'Donnell 12/15-Lipoxygenase Regulates the Inflammatory Response to Bacterial Products In Vivo J. Immunol., November 1, 2008; 181(9): 6514 - 6524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rosas, K. Liddiard, M. Kimberg, I. Faro-Trindade, J. U. McDonald, D. L. Williams, G. D. Brown, and P. R. Taylor The Induction of Inflammation by Dectin-1 In Vivo Is Dependent on Myeloid Cell Programming and the Progression of Phagocytosis J. Immunol., September 1, 2008; 181(5): 3549 - 3557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Adams, P. J. Rice, B. Graves, H. E. Ensley, H. Yu, G. D. Brown, S. Gordon, M. A. Monteiro, E. Papp-Szabo, D. W. Lowman, et al. Differential High-Affinity Interaction of Dectin-1 with Natural or Synthetic Glucans Is Dependent upon Primary Structure and Is Influenced by Polymer Chain Length and Side-Chain Branching J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 115 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. B. Shah, Y. Huang, R. Keshwara, T. Ozment-Skelton, D. L. Williams, and L. Keshvara {beta}-Glucan Activates Microglia without Inducing Cytokine Production in Dectin-1-Dependent Manner J. Immunol., March 1, 2008; 180(5): 2777 - 2785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Kelly, K. McNagny, D. L. Williams, N. van Rooijen, L. Maxwell, C. Gwozd, C. H. Mody, and P. Kubes The Lung Responds to Zymosan in a Unique Manner Independent of Toll-Like Receptors, Complement, and Dectin-1 Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 227 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Dennehy and G. D. Brown The role of the {beta}-glucan receptor Dectin-1 in control of fungal infection J. Leukoc. Biol., August 1, 2007; 82(2): 253 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. K. Chan, H. K. Wai Law, Z.-B. Lin, Y. L. Lau, and G. C.-F. Chan Response of human dendritic cells to different immunomodulatory polysaccharides derived from mushroom and barley Int. Immunol., July 2, 2007; (2007) dxm061v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Meyer-Wentrup, C. G. Figdor, M. Ansems, P. Brossart, M. D. Wright, G. J. Adema, and A. B. van Spriel Dectin-1 Interaction with Tetraspanin CD37 Inhibits IL-6 Production J. Immunol., January 1, 2007; 178(1): 154 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sato, X.-l. Yang, T. Yudate, J.-S. Chung, J. Wu, K. Luby-Phelps, R. P. Kimberly, D. Underhill, P. D. Cruz Jr., and K. Ariizumi Dectin-2 Is a Pattern Recognition Receptor for Fungi That Couples with the Fc Receptor {gamma} Chain to Induce Innate Immune Responses J. Biol. Chem., December 15, 2006; 281(50): 38854 - 38866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Lavigne, J. E. Albina, and J. S. Reichner beta-Glucan Is a Fungal Determinant for Adhesion-Dependent Human Neutrophil Functions J. Immunol., December 15, 2006; 177(12): 8667 - 8675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Gays, J. G. Aust, D. M. Reid, J. Falconer, N. Toyama-Sorimachi, P. R. Taylor, and C. G. Brooks Ly49B Is Expressed on Multiple Subpopulations of Myeloid Cells J. Immunol., November 1, 2006; 177(9): 5840 - 5851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yadav and J. S. Schorey The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria Blood, November 1, 2006; 108(9): 3168 - 3175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Carter, C. Thompson, D. M. Reid, S. Y. C. Wong, and D. F. Tough Preferential Induction of CD4+ T Cell Responses through In Vivo Targeting of Antigen to Dendritic Cell-Associated C-Type Lectin-1 J. Immunol., August 15, 2006; 177(4): 2276 - 2284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Ozment-Skelton, M. P. Goldman, S. Gordon, G. D. Brown, and D. L. Williams Prolonged Reduction of Leukocyte Membrane-Associated Dectin-1 Levels following beta-Glucan Administration J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 540 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Li, D. J. Allendorf, R. Hansen, J. Marroquin, C. Ding, D. E. Cramer, and J. Yan Yeast beta-Glucan Amplifies Phagocyte Killing of iC3b-Opsonized Tumor Cells via Complement Receptor 3-Syk-Phosphatidylinositol 3-Kinase Pathway J. Immunol., August 1, 2006; 177(3): 1661 - 1669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. M. Heinsbroek, P. R. Taylor, M. Rosas, J. A. Willment, D. L. Williams, S. Gordon, and G. D. Brown Expression of Functionally Different Dectin-1 Isoforms by Murine Macrophages J. Immunol., May 1, 2006; 176(9): 5513 - 5518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Palma, T. Feizi, Y. Zhang, M. S. Stoll, A. M. Lawson, E. Diaz-Rodriguez, M. A. Campanero-Rhodes, J. Costa, S. Gordon, G. D. Brown, et al. Ligands for the beta-Glucan Receptor, Dectin-1, Assigned Using "Designer" Microarrays of Oligosaccharide Probes (Neoglycolipids) Generated from Glucan Polysaccharides J. Biol. Chem., March 3, 2006; 281(9): 5771 - 5779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Suram, G. D. Brown, M. Ghosh, S. Gordon, R. Loper, P. R. Taylor, S. Akira, S. Uematsu, D. L. Williams, and C. C. Leslie Regulation of Cytosolic Phospholipase A2 Activation and Cyclooxygenase 2 Expression in Macrophages by the beta-Glucan Receptor J. Biol. Chem., March 3, 2006; 281(9): 5506 - 5514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Crowther and L. S. Schlesinger Endocytic pathway for surfactant protein A in human macrophages: binding, clathrin-mediated uptake, and trafficking through the endolysosomal pathway Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L334 - L342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Evans, P. Y. Hahn, F. McCann, T. J. Kottom, Z. V. Pavlovic', and A. H. Limper Pneumocystis Cell Wall {beta}-Glucans Stimulate Alveolar Epithelial Cell Chemokine Generation through Nuclear Factor-{kappa}B-Dependent Mechanisms Am. J. Respir. Cell Mol. Biol., June 1, 2005; 32(6): 490 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yoshitomi, N. Sakaguchi, K. Kobayashi, G. D. Brown, T. Tagami, T. Sakihama, K. Hirota, S. Tanaka, T. Nomura, I. Miki, et al. A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice J. Exp. Med., March 21, 2005; 201(6): 949 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Viriyakosol, J. Fierer, G. D. Brown, and T. N. Kirkland Innate Immunity to the Pathogenic Fungus Coccidioides posadasii Is Dependent on Toll-Like Receptor 2 and Dectin-1 Infect. Immun., March 1, 2005; 73(3): 1553 - 1560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Herre, A. S. J. Marshall, E. Caron, A. D. Edwards, D. L. Williams, E. Schweighoffer, V. Tybulewicz, C. R. e Sousa, S. Gordon, and G. D. Brown Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages Blood, December 15, 2004; 104(13): 4038 - 4045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Li, T. Yajima, K. Saito, H. Nishimura, T. Fushimi, Y. Ohshima, Y. Tsukamoto, and Y. Yoshikai Immunostimulating Properties of Intragastrically Administered Acetobacter-Derived Soluble Branched (1,4)-{beta}-D-Glucans Decrease Murine Susceptibility to Listeria monocytogenes Infect. Immun., December 1, 2004; 72(12): 7005 - 7011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nilsen, U. Nonstad, N. Khan, C. F. Knetter, S. Akira, A. Sundan, T. Espevik, and E. Lien Lipopolysaccharide and Double-stranded RNA Up-regulate Toll-like Receptor 2 Independently of Myeloid Differentiation Factor 88 J. Biol. Chem., September 17, 2004; 279(38): 39727 - 39735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Morales-Conde Laparoscopic Ventral Hernia Repair: Advances and Limitations Surgical Innovation, September 1, 2004; 11(3): 191 - 200. [Abstract] [PDF]
|
|
|
|
|
|
F. Hong, J. Yan, J. T. Baran, D. J. Allendorf, R. D. Hansen, G. R. Ostroff, P. X. Xing, N.-K. V. Cheung, and G. D. Ross Mechanism by Which Orally Administered {beta}-1,3-Glucans Enhance the Tumoricidal Activity of Antitumor Monoclonal Antibodies in Murine Tumor Models J. Immunol., July 15, 2004; 173(2): 797 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L. Tsikitis, N. A. Morin, E. O. Harrington, J. E. Albina, and J. S. Reichner The Lectin-Like Domain of Complement Receptor 3 Protects Endothelial Barrier Function from Activated Neutrophils J. Immunol., July 15, 2004; 173(2): 1284 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Adachi, T. Ishii, Y. Ikeda, A. Hoshino, H. Tamura, J. Aketagawa, S. Tanaka, and N. Ohno Characterization of {beta}-Glucan Recognition Site on C-Type Lectin, Dectin 1 Infect. Immun., July 1, 2004; 72(7): 4159 - 4171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Reid, M. Montoya, P. R. Taylor, P. Borrow, S. Gordon, G. D. Brown, and S. Y. C. Wong Expression of the {beta}-glucan receptor, Dectin-1, on murine leukocytes in situ correlates with its function in pathogen recognition and reveals potential roles in leukocyte interactions J. Leukoc. Biol., July 1, 2004; 76(1): 86 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Takeda and K. Okumura CAM and NK Cells Evid. Based Complement. Altern. Med., June 1, 2004; 1(1): 17 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.Y.K. Leung, C. Liu, L.F. Zhu, Y.Z. Hui, B. Yu, and K.P. Fung Chemical and biological characterization of a polysaccharide biological response modifier from Aloe vera L. var. chinensis (Haw.) Berg. Glycobiology, June 1, 2004; 14(6): 501 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. Borchers, C. L. Keen, and M. E. Gershwin Mushrooms, Tumors, and Immunity: An Update Experimental Biology and Medicine, May 1, 2004; 229(5): 393 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. J. Marshall, J. A. Willment, H.-H. Lin, D. L. Williams, S. Gordon, and G. D. Brown Identification and Characterization of a Novel Human Myeloid Inhibitory C-type Lectin-like Receptor (MICL) That Is Predominantly Expressed on Granulocytes and Monocytes J. Biol. Chem., April 9, 2004; 279(15): 14792 - 14802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. A. Whitten, I. F. Tew, B. L. Lee, and N. A. Ratcliffe A Novel Role for an Insect Apolipoprotein (Apolipophorin III) in {beta}-1,3-Glucan Pattern Recognition and Cellular Encapsulation Reactions J. Immunol., February 15, 2004; 172(4): 2177 - 2185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Taylor, G. D. Brown, J. Herre, D. L. Williams, J. A. Willment, and S. Gordon The Role of SIGNR1 and the {beta}-Glucan Receptor (Dectin-1) in the Nonopsonic Recognition of Yeast by Specific Macrophages J. Immunol., January 15, 2004; 172(2): 1157 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Romani, C. Montagnoli, S. Bozza, K. Perruccio, A. Spreca, P. Allavena, S. Verbeek, R. A. Calderone, F. Bistoni, and P. Puccetti The exploitation of distinct recognition receptors in dendritic cells determines the full range of host immune relationships with Candida albicans Int. Immunol., January 1, 2004; 16(1): 149 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Fernandez, M. Renedo, S. Alonso, and M. S. Crespo Release of Arachidonic Acid by Stimulation of Opsonic Receptors in Human Monocytes: THE Fc{gamma}R AND THE COMPLEMENT RECEPTOR 3 PATHWAYS J. Biol. Chem., December 26, 2003; 278(52): 52179 - 52187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Hong, R. D. Hansen, J. Yan, D. J. Allendorf, J. T. Baran, G. R. Ostroff, and G. D. Ross {beta}-Glucan Functions as an Adjuvant for Monoclonal Antibody Immunotherapy by Recruiting Tumoricidal Granulocytes as Killer Cells Cancer Res., December 15, 2003; 63(24): 9023 - 9031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. L. Ahren, E. Eriksson, A. Egesten, and K. Riesbeck Nontypeable Haemophilus influenzae Activates Human Eosinophils through {beta}-Glucan Receptors Am. J. Respir. Cell Mol. Biol., November 1, 2003; 29(5): 598 - 605. [Abstract] [Full Text]
|
|
|
|
|
|
K. Saito, T. Yajima, H. Nishimura, K. Aiba, R. Ishimitsu, T. Matsuguchi, T. Fushimi, Y. Ohshima, Y. Tsukamoto, and Y. Yoshikai Soluble Branched {beta}-(1,4)Glucans from Acetobacter Species Show Strong Activities to Induce Interleukin-12 in Vitro and Inhibit T-helper 2 Cellular Response with Immunoglobulin E Production in Vivo J. Biol. Chem., October 3, 2003; 278(40): 38571 - 38578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Aragane, A. Maeda, A. Schwarz, T. Tezuka, K. Ariizumi, and T. Schwarz Involvement of Dectin-2 in Ultraviolet Radiation-Induced Tolerance J. Immunol., October 1, 2003; 171(7): 3801 - 3807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. O'Reilly, C. M. Quinn, T. El-Shanawany, S. Gordon, and D. R. Greaves Multiple Ets Factors and Interferon Regulatory Factor-4 Modulate CD68 Expression in a Cell Type-specific Manner J. Biol. Chem., June 6, 2003; 278(24): 21909 - 21919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Capo, A. Moynault, Y. Collette, D. Olive, E. J. Brown, D. Raoult, and J.-L. Mege Coxiella burnetii Avoids Macrophage Phagocytosis by Interfering with Spatial Distribution of Complement Receptor 3 J. Immunol., April 15, 2003; 170(8): 4217 - 4225. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
and 
, respectively). Data are
expressed as the mean ± SD as a percentage of the binding to
control untreated M