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CUTTING EDGE |
Basel Institute for Immunology, Basel, Switzerland
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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and induces neutrophil
degranulation. Intracellularly, TREM-1 induces Ca2+
mobilization and tyrosine phosphorylation of
extracellular signal-related kinase 1 (ERK1), ERK2 and
phospholipase C-
. To mediate activation, TREM-1 associates with the
transmembrane adapter molecule DAP12. Thus, TREM-1 mediates activation
of neutrophil and monocytes, and may have a predominant role in
inflammatory responses. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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and TNF- (2). In
addition, engagement of these receptors can up-regulate or "prime"
the responsiveness of myeloid cells to other stimuli, potentiating the
inflammatory response (3).
Neutrophils and macrophages express additional activating receptors,
but their role in inflammation is unknown. These receptors belong
either to the Ig superfamily
(Ig-SF),3 such as
Ig-like transcripts (ILT)/leukocyte Ig-like receptors
(LIR)/monocyte/macrophage Ig-like receptors (MIRs), paired Ig-like
receptor (PIR-As), and signal regulatory protein ß1 (SIRPß1), or to
the C-type lectin superfamily, such as myeloid DAP12-associating
lectin-1 (MDL-1) (4, 5, 6, 7, 8). Typically, all of these receptors
bear some homology with activating NK cell receptors (9).
In particular, they contain a short intracellular domain that lacks
docking motifs for signaling mediators and a transmembrane domain with
a positively charged amino acid residue. This residue allows pairing
with transmembrane adapter proteins, which contain a negatively charged
amino acid in the transmembrane domain and a cytoplasmic immunoreceptor
tyrosine-based activation motif (ITAM). Specifically, ILT/LIR/MIR and
PIRs are coupled with the -chain of the Fc receptors (FcR)
(4, 5, 6), whereas SIRPß1 and MDL-1 pair with DAP12
(7, 8). Upon ITAM phosphorylation, these
adapters recruit protein tyrosine kinases, which initiate a cascade of
phosphorylation events that ultimately lead to cell
activation.
The recent discovery of a new DAP12-associated receptor on NK cells, called NKp44 (10), suggested the possible existence of yet unknown DAP12-associated receptors also on other cells involved in innate responses. By screening a cDNA sequence database with the NKp44 polypeptide, we have identified new Ig-SF receptors exclusively expressed on myeloid cells, that were designated TREM (triggering receptor expressed on myeloid cells). Here we show that one of these receptors, TREM-1, stimulates neutrophil and monocyte-mediated inflammatory responses.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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GenBank expressed sequence tagged database (dbEST) was searched with the amino acid sequences of NKp44 using the tblastn algorithm. A contig assembled from 17 distinct cDNAs (accession nos. D78812, AI337247, AW139572, AW274906, AW139573, AI394041, AI621023, AI186456, AI968134, AI394092, AI681036, AI962750, AA494171, AA099288, AW139363, AW135801, AA101983) contained an open reading frame encoding TREM-1. Search of the dbEST with the complete TREM-1 open reading frame matched to one related sequence referred to as TREM-2 (accession no. N41388).
RT-PCR
The 
760-bp TREM-1 and 1000-bp TREM-2 cDNAs were amplified
by RT-PCR, cloned into pCR2.1 (Invitrogen, Carlsbad, CA), and
sequenced. PCR primers were: TREM-1, 5'-GCTGGTGCACAGGAAGGATG,
3'-GGCTGGAAGTCAGAGGACATT; and TREM-2, 5'-TGATCCTCTCTTTTCTGCAG,
3'-GTGTTTAAAATGTCCAATATT.
Cells
Human blood was mixed with one volume of 3% Dextran T-500 (Pharmacia, Uppsala, Sweden) in 0.9% NaCl to sediment erythrocytes. Leukocytes in the supernatant were further separated by gradient density centrifugation on Lymphocyte Separation Medium (ICN Biomedicals/Cappel, Aurora, OH) into PBMCs and neutrophils. CD14+ monocytes were purified from PBMCs by magnetic cell sorting using CD14 MicroBeads (Miltenyi, Bergisch Gladbach, Germany).
Production of TREM-1 human Fc (TREM-1-Fc) fusion protein and anti-TREM-1 mAbs
To produce soluble TREM-1-Fc, the cDNA fragment encoding the TREM-1 extracellular region was amplified by PCR and cloned into an expression vector containing the exons for hinge, CH2, and CH3 region of human IgG1. Transfection of the chimeric gene into the mouse myeloma cell line J558L, screening of culture supernatants, and purification of TREM-1-Fc were performed as previously described (11). Anti-TREM-1 mAbs were produced by immunizing BALB/c mice with TREM-1-Fc as reported elsewhere (12).
Transient transfections
TREM-1 and TREM-2 were subcloned into pCMV-1-FLAG (Kodak) and expressed as amino-terminal FLAG peptide fusion proteins in COS-7 cells. DAP12 was subcloned into pHM6 (Boehringer Mannheim, Mannheim, Germany) and expressed as amino-terminal hemagglutinin (HA) peptide fusion protein in COS-7 cells. Transient transfections were performed as previously described (4). Cell surface expression of transfected cDNAs was determined by FACS analysis with anti-FLAG (Kodak), anti-HA (Boehringer Mannheim), and 21C7 mAbs.
Abs, stainings, and FACS analysis
Before staining, all cells were incubated with PBS/20% human serum for 1 h on ice to block Fc receptors. Whole blood leukocytes were incubated with mAbs 21C7 (anti-TREM-1, IgG1), 3C10 (anti-CD14, IgG2b), and L243 (anti-HLA-DR, IgG2a) followed by isotype-specific FITC/PE/biotin-conjugated secondary Abs. After a further incubation step with APC-labeled streptavidin, cells were analyzed by FACS. Monocytes and neutrophils stimulated with LPS (1 µg/ml) for 16 h were stained with either mAb 21C7 or mAb 1B7.11 (control IgG1, anti-2,4,6-trinitrophenyl (TNP); American Type Culture Collection, Manassas, VA), followed by human-adsorbed PE-conjugated goat anti-mouse IgG.
Measurement of cytokines, chemokines, degranulation, and cell surface activation markers
Purified monocytes or neutrophils were stimulated for 24 h
in 96-well flat-bottom plates coated with F(ab')2
goat anti-mouse IgG (5 µg/ml) followed by either 21C7, 1F11
(anti-MHC class I), or 1B7.11 (anti-TNP) mAbs. Cells were
plated at a concentration of 5 x 104
cells/well in the presence or absence of LPS (1 µg/ml). Supernatants
were collected and tested for production of IL-6, IL-8, IL-10,
IL-12p75, monocyte chemoattractant protein-1 (MCP-1), TNF-, and
myeloperoxidase (MPO) by ELISA (PharMingen, San Diego, CA). To measure
the expression of cell surface markers, monocytes and neutrophils were
stimulated as described above and, after 48h, were stained with PE- or
FITC-conjugated anti-CD11b, anti-CD11c, anti-CD18,
anti-CD29, anti-CD32, anti-CD40, anti-CD49d,
anti-CD49e, anti-CD54, anti-CD80, anti-CD83, or
anti-CD86, (all from Immunotech, Marseille, France) and analyzed
by FACS.
Measurement of cytosolic Ca2+ and biochemical analysis
Determination of intracellular Ca2+
mobilization was done according to previous reports (4).
Determination of protein tyrosine phosphorylation,
mitogen activated protein kinase activation, phospholipase C-
(PLC-) phosphorylation, and immunoprecipitations
were performed as previously described (7).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The GenBank EST data base was searched with NKp44 polypeptide, and
several overlapping cDNAs were found. These were assembled in a contig
which contained an open reading frame en-coding a protein of 234 aa
with a predicted molecular mass of 26 kDa (Fig. 1
, upper
panel). The amino acid sequence
begins with a hydrophobic signal peptide followed by an extracellular
region composed of a single Ig-SF domain containing three potential
N-glycosylation sites. The length of the Ig-type fold and
the characteristic pattern Asp-Xaa-Gly-Xaa-Tyr-Xaa-Cys in the region
leading to the ß-strand F indicate that the Ig-type fold is of the
V-type. The putative transmembrane domain contains a charged lysine
residue and is followed by a cytoplasmic tail of 5 aa with no signaling
motifs. Similar transmembrane and cytoplasmic domains are present in
activating NK cell receptors which pair with the transmembrane adapter
protein DAP12 (9). A cDNA containing the entire open
reading frame was amplified by RT-PCR from monocytes and neutrophils,
but not from lymphocytes or other cell types (data not shown).
Therefore, we designated this molecule TREM-1. The GenBank EST database
was then searched with TREM-1 polypeptide, and a novel cDNA encoding a
TREM-1-homologue was identified. We designated this molecule TREM-2
(Fig. 1, lower panel). The alignment of TREM-1, TREM-2, and
NKp44 extracellular domains revealed 20% identity (data not shown).
Analysis of somatic cell hybrids containing different human chromosomes
demonstrated that the genes encoding TREMs maps on human chromosome 6,
like the NKp44 gene (data not shown).
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To investigate the cellular distribution of TREM-1, we produced
the anti-TREM-1 mAb 21C7. As shown in Fig. 2A, mAb 21C7 stained
TREM-1-transfected COS-7 cells, as compared with control transfectants.
In addition, expression of TREM-1 was partially increased by
cotransfection of DAP12 cDNA, suggesting that cell surface expression
of TREM-1 may require association with either DAP12 or a related
signaling molecule. In peripheral blood of different donors, 21C7
stained neutrophils and, to a lower extent,
CD14high monocytes. CD14dim
monocytes, dendritic cells (DCs) or lymphocytes were TREM-1 negative
(Fig. 2B). We further investigated the expression of TREM-1
during differentiation of CD14+ monocytes into
either DCs or macrophages in the presence of GM-CSF/IL-4 or M-CSF,
respectively. TREM-1 was completely down-regulated on these cells after
3 days of culture (data not shown). Stimulation of DCs with LPS,
heat-inactivated Gram-positive bacteria, Gram-negative bacteria, or
fungi did not induce TREM-1 expression (data not shown). In striking
contrast, these stimuli induced strong up-regulation of TREM-1 on
neutrophils and monocytes (Fig. 2C and data not shown). This
selective expression of TREM-1 on neutrophils and monocytes and its
induction by pathogens suggested that it may play a role in acute
inflammatory responses.
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To examine whether TREM-1 can trigger acute inflammatory
responses, neutrophils and monocytes were plated on a plastic surface
coated with F(ab')2 goat anti-mouse IgG and
the mAb 21C7 and tested for secretion of chemokines and cytokines and
for release of granule components. In neutrophils, cross-linking of
TREM-1 induced secretion of IL-8 and release of MPO (Fig. 3, A and B). This
latter release was strongly potentiated following priming of
neutrophils with LPS (Fig. 3C). In monocytes, cross-linking
of TREM-1 generated release of large amounts of IL-8 as well as MCP-1
and TNF- (Fig. 3, D–F). TNF- and MCP-1 secretion was
strongly up-regulated by LPS-mediated priming (Fig. 3, G–H), further demonstrating the importance of bacterial
costimuli for TREM-1-mediated activation. In control experiments,
neutrophils and monocytes were stimulated with isotype-matched Abs
which either bind (such as anti-MHC class I mAbs) or do not bind
(such as an anti-TNP mAb) cells. In both cases, secretion of
cytokines, chemokines, and MPO was 5- to 50-fold lower than that
induced via TREM-1 (Fig. 3 and data not shown). Thus, activation of
neutrophils and monocytes triggered by anti-TREM-1 mAb is not due
to engagement of Fc receptors. Secretion of cytokines important for the
adaptive immune response, such as IL-6, IL-10, IL-12, or for
surveillance against viral infections, such as type I IFN, were not
significantly increased by engagement of TREM-1 (data not shown).
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, cell surface expression
of CD29, CD11c, and CD49e, and to a lesser extent CD11b, CD49d, and
CD18 were increased on both neutrophils and monocytes. Thus, TREM-1 may
increase cellular adhesion to fibronectin, fibrinogen, and VCAM by
up-regulating CD11b/CD18 (Mac-1), CD29/CD49d, and CD29/CD49e
heterodimers, respectively. In addition, TREM-1 stimulation led to a
strong up-regulation of the costimulatory molecules CD40, CD86 (B7.2),
and CD54 (ICAM-1), as well as of CD83 and CD32 (FcRII) on monocytes.
Thus, TREM-1 is not only capable of increasing adhesion of myeloid
cells to endothelium and extracellular matrix molecules but can also
prepare monocytes for costimulation of other cells recruited to the
inflammatory lesions.
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Activation of neutrophils and monocytes is often accompanied by a
number of intracellular changes. Indeed, ligation of TREM-1 with the
mAb 21C7 elicited a rapid rise in intracellular
Ca2+ concentration (Fig. 4A). In addition,
cross-linking of TREM-1 stimulated tyrosine
phosphorylation of several proteins with apparent
molecular masses of 40, 60, 70, and 100 kDa (Fig. 4B). The observed 40-kDa tyrosine
phosphorylated proteins correspond to mitogen activated
protein kinases, as demonstrated by anti-phospho-ERK1/2
immunoblotting (Fig. 4C). Precipitation of tyrosine
phosphorylated proteins and immunoblotting with an
anti-PLC- Ab, revealed that the observed 100-kDa
phosphoprotein corresponds to PLC- (Fig. 4D), thus
explaining the observed Ca2+ influx.
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30-kDa glycoprotein associated with DAP12
Biochemical analysis of TREM-1 immunoprecipitated from
surface-biotinylated monocytes revealed that TREM-1 is a glycoprotein
of 30 kDa, which is reduced to 26 kDa after
N-deglycosylation, in agreement with the predicted molecular
mass of TREM-1 (Fig. 5A).
Because TREM-1 lacks known signaling motifs in the cytoplasmic domain,
it should associate with a separate signal transduction subunit to
mediate activating signals. Adapter molecules, such as DAP12, are
tyrosine phosphorylated upon cell treatment with the
phosphatase-inhibitor pervanadate (9). Indeed,
anti-phosphotyrosine blotting of TREM-1 immunoprecipitates from
pervanadate-stimulated monocytes revealed a phosphorylated
protein of 12 kDa and 24 kDa under reducing and nonreducing
conditions, respectively (Fig. 5B). An identical pattern was
observed after immunoprecipitation of SIRPß1, which is associated
with DAP12 (7). Indeed, immunoblotting of TREM-1
immunoprecipitates with anti-DAP12 demonstrated that TREM-1
associates with DAP12 (Fig. 5C).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In addition to TREM-1, we have cloned a novel cDNA encoding a
TREM-1-homologue, called TREM-2 (Fig. 1
). Because TREM-2 is expressed
on macrophages and DCs but not on granulocytes or monocytes (data not
shown), it may have a role in chronic inflammations and may stimulate
production of constitutive rather than inflammatory chemokines and
cytokines. Thus, distinct TREM receptors may regulate acute and chronic
inflammatory responses, allowing myeloid cells to mount distinct types
of responses to different Ags. Both TREM-1 and TREM-2 display
some sequence homology with activating NK cell receptors, such as NKp44
(10). All of these molecules display a single V-type
Ig-like extracellular domain and associate with DAP12 to induce
activation. In addition, they are encoded by genes on human chromosome
6. Thus, this chromosome may contain a gene cluster encoding
structurally related receptors that activate cell types involved in
different innate responses.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Marco Colonna, Basel Institute for Immunology, 487 Grenzacherstrasse, CH-4005 Basel, Switzerland.
3 Abbreviations used in this paper: Ig-SF, Ig superfamily; SIRPß1, signal regulatory protein ß1; TREM, triggering receptor expressed on myeloid cells; HA, hemagglutinin; TNP, 2,4,6-trinitrophenyl; MCP, monocyte chemoattractant protein; PLC-, phospholipase C-; DC, dendritic cell; MPO, myeloperoxidase; ITAM, immunoreceptor tyrosine-based activation motif; ERK, extracellular signal-related kinase.
Received for publication January 12, 2000. Accepted for publication March 14, 2000.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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|
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|
 |
|
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|
|
|
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 K. Kofoed, U. V. Schneider, T. Scheel, O. Andersen, and J. Eugen-Olsen Development and Validation of a Multiplex Add-On Assay for Sepsis Biomarkers Using xMAP Technology Clin. Chem., July 1, 2006; 52(7): 1284 - 1293. [Abstract] [Full Text] [PDF]
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R. G. King, B. R. Herrin, and L. B. Justement Trem-Like Transcript 2 Is Expressed on Cells of the Myeloid/Granuloid and B Lymphoid Lineage and Is Up-Regulated in Response to Inflammation J. Immunol., May 15, 2006; 176(10): 6012 - 6021. [Abstract] [Full Text] [PDF]
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S. Gibot, C. Buonsanti, F. Massin, M. Romano, M.-N. Kolopp-Sarda, F. Benigni, G. C. Faure, M.-C. Bene, P. Panina-Bordignon, N. Passini, et al. Modulation of the triggering receptor expressed on the myeloid cell type 1 pathway in murine septic shock. Infect. Immun., May 1, 2006; 74(5): 2823 - 2830. [Abstract] [Full Text] [PDF]
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 A. M. Mahdy, D. A. Lowes, H. F. Galley, J. E. Bruce, and N. R. Webster Production of Soluble Triggering Receptor Expressed on Myeloid Cells by Lipopolysaccharide-Stimulated Human Neutrophils Involves De Novo Protein Synthesis Clin. Vaccine Immunol., April 1, 2006; 13(4): 492 - 495. [Abstract] [Full Text] [PDF]
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E. Merck, C. Gaillard, M. Scuiller, P. Scapini, M. A. Cassatella, G. Trinchieri, and E. E. M. Bates Ligation of the FcR{gamma} Chain-Associated Human Osteoclast-Associated Receptor Enhances the Proinflammatory Responses of Human Monocytes and Neutrophils. J. Immunol., March 1, 2006; 176(5): 3149 - 3156. [Abstract] [Full Text] [PDF]
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K. J. Carpenter, K. F. Buckland, Z. Xing, and C. M. Hogaboam Intrapulmonary, Adenovirus-Mediated Overexpression of KARAP/DAP12 Enhances Fungal Clearance during Invasive Aspergillosis Infect. Immun., December 1, 2005; 73(12): 8402 - 8406. [Abstract] [Full Text] [PDF]
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A. Fuchs, M. Cella, T. Kondo, and M. Colonna Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44 Blood, September 15, 2005; 106(6): 2076 - 2082. [Abstract] [Full Text] [PDF]
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I. R. Turnbull, J. E. McDunn, T. Takai, R. R. Townsend, J. P. Cobb, and M. Colonna DAP12 (KARAP) amplifies inflammation and increases mortality from endotoxemia and septic peritonitis J. Exp. Med., August 1, 2005; 202(3): 363 - 369. [Abstract] [Full Text] [PDF]
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 H. H. Klunemann, B. H. Ridha, L. Magy, J. R. Wherrett, D. M. Hemelsoet, R. W. Keen, J. L. De Bleecker, M. N. Rossor, J. Marienhagen, H. E. Klein, et al. The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2 Neurology, May 10, 2005; 64(9): 1502 - 1507. [Abstract] [Full Text] [PDF]
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E. Merck, B. de Saint-Vis, M. Scuiller, C. Gaillard, C. Caux, G. Trinchieri, and E. E. M. Bates Fc receptor {gamma}-chain activation via hOSCAR induces survival and maturation of dendritic cells and modulates Toll-like receptor responses Blood, May 1, 2005; 105(9): 3623 - 3632. [Abstract] [Full Text] [PDF]
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M. R.-E.-I. Benhnia, D. Wroblewski, M. N. Akhtar, R. A. Patel, W. Lavezzi, S. C. Gangloff, S. M. Goyert, M. J. Caimano, J. D. Radolf, and T. J. Sellati Signaling through CD14 Attenuates the Inflammatory Response to Borrelia burgdorferi, the Agent of Lyme Disease J. Immunol., February 1, 2005; 174(3): 1539 - 1548. [Abstract] [Full Text] [PDF]
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M. Schenk, A. Bouchon, S. Birrer, M. Colonna, and C. Mueller Macrophages Expressing Triggering Receptor Expressed on Myeloid Cells-1 Are Underrepresented in the Human Intestine J. Immunol., January 1, 2005; 174(1): 517 - 524. [Abstract] [Full Text] [PDF]
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D. Voehringer, D. B. Rosen, L. L. Lanier, and R. M. Locksley CD200 Receptor Family Members Represent Novel DAP12-associated Activating Receptors on Basophils and Mast Cells J. Biol. Chem., December 24, 2004; 279(52): 54117 - 54123. [Abstract] [Full Text] [PDF]
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 A. Roumier, C. Bechade, J.-C. Poncer, K.-H. Smalla, E. Tomasello, E. Vivier, E. D. Gundelfinger, A. Triller, and A. Bessis Impaired Synaptic Function in the Microglial KARAP/DAP12-Deficient Mouse J. Neurosci., December 15, 2004; 24(50): 11421 - 11428. [Abstract] [Full Text] [PDF]
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S. Knapp, S. Gibot, A. de Vos, H. H. Versteeg, M. Colonna, and T. van der Poll Cutting Edge: Expression Patterns of Surface and Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Human Endotoxemia J. Immunol., December 15, 2004; 173(12): 7131 - 7134. [Abstract] [Full Text] [PDF]
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S. Gibot, M.-N. Kolopp-Sarda, M.-C. Bene, P.-E. Bollaert, A. Lozniewski, F. Mory, B. Levy, and G. C. Faure A Soluble Form of the Triggering Receptor Expressed on Myeloid Cells-1 Modulates the Inflammatory Response in Murine Sepsis J. Exp. Med., December 6, 2004; 200(11): 1419 - 1426. [Abstract] [Full Text] [PDF]
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H. Aguilar, D. Alvarez-Errico, A. C. Garcia-Montero, A. Orfao, J. Sayos, and M. Lopez-Botet Molecular Characterization of a Novel Immune Receptor Restricted to the Monocytic Lineage J. Immunol., December 1, 2004; 173(11): 6703 - 6711. [Abstract] [Full Text] [PDF]
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E. Merck, C. Gaillard, D. M. Gorman, F. Montero-Julian, I. Durand, S. M. Zurawski, C. Menetrier-Caux, G. Carra, S. Lebecque, G. Trinchieri, et al. OSCAR is an FcR{gamma}-associated receptor that is expressed by myeloid cells and is involved in antigen presentation and activation of human dendritic cells Blood, September 1, 2004; 104(5): 1386 - 1395. [Abstract] [Full Text] [PDF]
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A. V. Washington, R. L. Schubert, L. Quigley, T. Disipio, R. Feltz, E. H. Cho, and D. W. McVicar A TREM family member, TLT-1, is found exclusively in the {alpha}-granules of megakaryocytes and platelets Blood, August 15, 2004; 104(4): 1042 - 1047. [Abstract] [Full Text] [PDF]
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L. Richeldi, M. Mariani, M. Losi, F. Maselli, L. Corbetta, C. Buonsanti, M. Colonna, F. Sinigaglia, P. Panina-Bordignon, and L.M. Fabbri Triggering receptor expressed on myeloid cells: role in the diagnosis of lung infections Eur. Respir. J., August 1, 2004; 24(2): 247 - 250. [Abstract] [Full Text] [PDF]
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 S. Gibot and A. Cravoisy Soluble Form of the Triggering Receptor Expressed on Myeloid Cells-1 as a Marker of Microbial Infection Clin. Med. Res., August 1, 2004; 2(3): 181 - 187. [Abstract] [Full Text] [PDF]
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 S. Gibot, M.-N. Kolopp-Sarda, M. C. Bene, A. Cravoisy, B. Levy, G. C. Faure, and P.-E. Bollaert Plasma Level of a Triggering Receptor Expressed on Myeloid Cells-1: Its Diagnostic Accuracy in Patients with Suspected Sepsis Ann Intern Med, July 6, 2004; 141(1): 9 - 15. [Abstract] [Full Text] [PDF]
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S. Ishikawa, N. Arase, T. Suenaga, Y. Saita, M. Noda, T. Kuriyama, H. Arase, and T. Saito Involvement of FcR{gamma} in signal transduction of osteoclast-associated receptor (OSCAR) Int. Immunol., July 1, 2004; 16(7): 1019 - 1025. [Abstract] [Full Text] [PDF]
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M. Terme, E. Tomasello, K. Maruyama, F. Crepineau, N. Chaput, C. Flament, J.-P. Marolleau, E. Angevin, E. F. Wagner, B. Salomon, et al. IL-4 Confers NK Stimulatory Capacity to Murine Dendritic Cells: A Signaling Pathway Involving KARAP/DAP12-Triggering Receptor Expressed on Myeloid Cell 2 Molecules J. Immunol., May 15, 2004; 172(10): 5957 - 5966. [Abstract] [Full Text] [PDF]
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N. Aoki, A. Zganiacz, P. Margetts, and Z. Xing Differential Regulation of DAP12 and Molecules Associated with DAP12 during Host Responses to Mycobacterial Infection Infect. Immun., May 1, 2004; 72(5): 2477 - 2483. [Abstract] [Full Text] [PDF]
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M. P. Radsak, H. R. Salih, H.-G. Rammensee, and H. Schild Triggering Receptor Expressed on Myeloid Cells-1 in Neutrophil Inflammatory Responses: Differential Regulation of Activation and Survival J. Immunol., April 15, 2004; 172(8): 4956 - 4963. [Abstract] [Full Text] [PDF]
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K. E. Nichols, K. Haines, P. S. Myung, S. Newbrough, E. Myers, H. Jumaa, D. J. Shedlock, H. Shen, and G. A. Koretzky Macrophage activation and Fc{gamma} receptor-mediated signaling do not require expression of the SLP-76 and SLP-65 adaptors J. Leukoc. Biol., March 1, 2004; 75(3): 541 - 552. [Abstract] [Full Text] [PDF]
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N. A. Begum, K. Ishii, M. Kurita-Taniguchi, M. Tanabe, M. Kobayashi, Y. Moriwaki, M. Matsumoto, Y. Fukumori, I. Azuma, K. Toyoshima, et al. Mycobacterium bovis BCG Cell Wall-Specific Differentially Expressed Genes Identified by Differential Display and cDNA Subtraction in Human Macrophages Infect. Immun., February 1, 2004; 72(2): 937 - 948. [Abstract] [Full Text] [PDF]
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 S. Gibot, A. Cravoisy, B. Levy, M.-C. Bene, G. Faure, and P.-E. Bollaert Soluble Triggering Receptor Expressed on Myeloid Cells and the Diagnosis of Pneumonia N. Engl. J. Med., January 29, 2004; 350(5): 451 - 458. [Abstract] [Full Text] [PDF]
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D.-H. Chung, M. B. Humphrey, M. C. Nakamura, D. G. Ginzinger, W. E. Seaman, and M. R. Daws CMRF-35-Like Molecule-1, a Novel Mouse Myeloid Receptor, Can Inhibit Osteoclast Formation J. Immunol., December 15, 2003; 171(12): 6541 - 6548. [Abstract] [Full Text] [PDF]
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J. Paloneva, J. Mandelin, A. Kiialainen, T. Bohling, J. Prudlo, P. Hakola, M. Haltia, Y. T. Konttinen, and L. Peltonen DAP12/TREM2 Deficiency Results in Impaired Osteoclast Differentiation and Osteoporotic Features J. Exp. Med., August 18, 2003; 198(4): 669 - 675. [Abstract] [Full Text] [PDF]
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K. Yotsumoto, Y. Okoshi, K. Shibuya, S. Yamazaki, S. Tahara-Hanaoka, S.-i. Honda, M. Osawa, A. Kuroiwa, Y. Matsuda, D. G. Tenen, et al. Paired Activating and Inhibitory Immunoglobulin-like Receptors, MAIR-I and MAIR-II, Regulate Mast Cell and Macrophage Activation J. Exp. Med., July 21, 2003; 198(2): 223 - 233. [Abstract] [Full Text] [PDF]
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M. R. Daws, P. M. Sullam, E. C. Niemi, T. T. Chen, N. K. Tchao, and W. E. Seaman Pattern Recognition by TREM-2: Binding of Anionic Ligands J. Immunol., July 15, 2003; 171(2): 594 - 599. [Abstract] [Full Text] [PDF]
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J. Yang, G. Hu, S.-W. Wang, Y. Li, R. Martin, K. Li, and Z. Yao Calcineurin/Nuclear Factors of Activated T Cells (NFAT)-activating and Immunoreceptor Tyrosine-based Activation Motif (ITAM)-containing Protein (CNAIP), a Novel ITAM-containing Protein That Activates the Calcineurin/NFAT-signaling Pathway J. Biol. Chem., May 2, 2003; 278(19): 16797 - 16801. [Abstract] [Full Text] [PDF]
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J. R. Bleharski, V. Kiessler, C. Buonsanti, P. A. Sieling, S. Stenger, M. Colonna, and R. L. Modlin A Role for Triggering Receptor Expressed on Myeloid Cells-1 in Host Defense During the Early-Induced and Adaptive Phases of the Immune Response J. Immunol., April 1, 2003; 170(7): 3812 - 3818. [Abstract] [Full Text] [PDF]
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 H. Nochi, N. Aoki, K. Oikawa, M. Yanai, Y. Takiyama, Y. Atsuta, H. Kobayashi, K. Sato, M. Tateno, T. Matsuno, et al. Modulation of Hepatic Granulomatous Responses by Transgene Expression of DAP12 or TREM-1-Ig Molecules Am. J. Pathol., April 1, 2003; 162(4): 1191 - 1201. [Abstract] [Full Text] [PDF]
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 J. Macdonald, H. F. Galley, and N. R. Webster Oxidative stress and gene expression in sepsis Br. J. Anaesth., February 1, 2003; 90(2): 221 - 232. [Abstract] [Full Text] [PDF]
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A. V. Washington, L. Quigley, and D. W. McVicar Initial characterization of TREM-like transcript (TLT)-1: a putative inhibitory receptor within the TREM cluster Blood, November 15, 2002; 100(10): 3822 - 3824. [Abstract] [Full Text] [PDF]
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G. W. Henkel, S. R. McKercher, and R. A. Maki Identification of three genes up-regulated in PU.1 rescued monocytic precursor cells Int. Immunol., July 1, 2002; 14(7): 723 - 732. [Abstract] [Full Text] [PDF]
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D. Mason, P. Andre, A. Bensussan, C. Buckley, C. Civin, E. Clark, M. de Haas, S. Goyert, M. Hadam, D. Hart, et al. CD antigens 2002 Blood, May 15, 2002; 99(10): 3877 - 3880. [Full Text] [PDF]
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D. Mason, P. Andre, A. Bensussan, C. Buckley, C. Civin, E. Clark, M. de Haas, S. Goyert, M. Hadam, D. Hart, et al. CD antigens 2001 J. Leukoc. Biol., November 1, 2001; 70(5): 685 - 690. [Abstract] [Full Text] [PDF]
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A. Bouchon, C. Hernandez-Munain, M. Cella, and M. Colonna A Dap12-Mediated Pathway Regulates Expression of Cc Chemokine Receptor 7 and Maturation of Human Dendritic Cells J. Exp. Med., October 15, 2001; 194(8): 1111 - 1122. [Abstract] [Full Text] [PDF]
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N. Aoki, S. Kimura, Y. Takiyama, Y. Atsuta, A. Abe, K. Sato, and M. Katagiri The Role of the DAP12 Signal in Mouse Myeloid Differentiation J. Immunol., October 1, 2000; 165(7): 3790 - 3796. [Abstract] [Full Text] [PDF]
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