| 1999 |
CD300a (IRp60) is an inhibitory receptor on NK cells that, upon tyrosine phosphorylation (induced by sodium pervanadate), associates with the SH2-containing phosphatases SHP-1 and SHP-2, thereby inhibiting NK cell cytotoxicity. |
Monoclonal antibody generation, cross-linking assays, co-immunoprecipitation after pervanadate treatment |
European journal of immunology |
High |
10540326
|
| 2000 |
CD300a (CMRF-35H) gene is located on human chromosome 17, encodes a single V-type Ig-like domain extracellular protein with three ITIMs in its cytoplasmic tail, and spans ~12 kb with seven exons. |
Genomic clone isolation, intron-exon organization mapping, chromosomal mapping |
Tissue antigens |
High |
10746781
|
| 2005 |
CD300a (IRp60) cross-linking on human mast cells inhibits IgE-induced degranulation and SCF-mediated survival via tyrosine phosphorylation, phosphatase recruitment (SHP-1/SHP-2), and termination of cellular calcium influx. |
Cross-linking with monoclonal antibodies, flow cytometry (Ca2+ flux), tryptase/IL-4 release assays, murine allergic peritonitis model with CD300a neutralization |
Journal of immunology |
High |
16339535
|
| 2005 |
CD300a (IRp60) cross-linking on human eosinophils inhibits IL-5-mediated JAK2 phosphorylation and eotaxin/IL-5/GM-CSF-mediated ERK1/2 and p38 phosphorylation; CD300a undergoes tyrosine phosphorylation and recruits SHP-1 but not SHP-2 in eosinophils. |
Cross-linking assays, Western blotting for phosphorylation, transmigration assays, cytokine/apoptosis assays |
Blood |
High |
16254138
|
| 2006 |
CD300a co-aggregation with IgE receptor (via bispecific antibody) inhibits IgE-mediated mast cell degranulation by inhibiting FcεRI signaling events including calcium influx; linkage of CD300a to CCR3 similarly inhibits eosinophil and mast cell activation and reverses airway inflammation in a chronic asthma model. |
Bispecific antibody fragment generation, phosphorylation/calcium flux FACS, degranulation assays, murine passive cutaneous anaphylaxis and airway inflammation models |
Journal of allergy and clinical immunology |
High |
16750992 17088133
|
| 2006 |
CD300a extracellular domain adopts a monomeric immunoglobulin-like fold in solution, as determined by SAXS and homology modeling. |
Recombinant protein expression/refolding from E. coli, small-angle X-ray scattering (SAXS), homology modeling |
International journal of biological macromolecules |
Medium |
16949664
|
| 2007 |
CD300a surface expression on human neutrophils is rapidly increased by LPS and GM-CSF via translocation of an intracellular pool to the cell surface; co-ligation of CD300a with FcγRIIa (CD32a) inhibits FcγRIIa-mediated signaling selectively without inhibiting TLR4-mediated ROS production. |
Flow cytometry, HL-60 differentiation model, co-ligation assays |
Molecular immunology |
Medium |
17588661
|
| 2008 |
CD300a co-aggregation with Kit (CD117) via bispecific antibody inhibits SCF-induced signaling in mast cells, which is mediated by Kit-driven tyrosine phosphorylation of CD300a and recruitment of SHIP-1 (but not SHP-1); this impairs mast cell differentiation, survival, and activation. |
Bispecific antibody library, co-immunoprecipitation, Western blotting, in vitro differentiation/survival assays, murine cutaneous anaphylaxis model |
Journal of immunology |
High |
18424727
|
| 2008 |
CD300a/c triggering on plasmacytoid dendritic cells reduces TNF-α and increases IFN-α secretion in response to TLR7/9 ligands; IFN-α feeds back to down-regulate CD300a/c expression. |
Cross-linking antibody stimulation, cytokine ELISA, neutralizing antibody experiments |
Blood |
Medium |
18535206
|
| 2011 |
CD300a extracellular domain (as Fc fusion protein) specifically binds phosphatidylserine (PS) exposed on apoptotic cells; PS binding induces SHP-1 recruitment by CD300a in mast cells in response to LPS. |
CD300a-Fc fusion protein, binding assay to apoptotic cells, SHP-1 co-immunoprecipitation |
Biochemical and biophysical research communications |
High |
22185693
|
| 2011 |
CD300a co-ligation with BCR on B cells inhibits Ca2+ mobilization and NFAT transcriptional activity; siRNA knockdown of CD300a increases BCR-mediated proliferation, confirming its inhibitory capacity. |
Co-ligation assays, calcium mobilization FACS, NFAT reporter assay, siRNA knockdown, proliferation assays |
Blood |
High |
21482706
|
| 2012 |
CD300a binds phosphatidylethanolamine (PE) and phosphatidylserine (PS) on dead cells; mutational studies identified residues forming a cavity in the IgV domain where PE/PS hydrophilic heads penetrate; CD300a down-regulates macrophage phagocytosis of apoptotic cells and its ectopic expression in CD300a-negative lines decreases engulfment. |
Surface plasmon resonance, ultracentrifugation, ELISA, reporter cell assays, site-directed mutagenesis, structural modeling, phagocytosis assays |
Blood |
High |
22302738
|
| 2012 |
CD300a is a non-phagocytic PS receptor on mast cells that delivers an inhibitory signal suppressing LPS-induced inflammatory cytokine and chemokine production; after apoptotic cell accumulation in vivo (cecal ligation and puncture), CD300a-PS interaction suppresses neutrophil chemoattractant release from mast cells. |
CD300a-deficient mice, peritoneal mast cell isolation, cytokine/chemokine measurement, CLP model, antibody blockade of CD300a-PS interaction |
Journal of experimental medicine |
High |
22826299
|
| 2012 |
CD300a ITIM tyrosine phosphorylation requires the src kinase Lck; phosphorylated ITIMs dock both SHP-1 and SHP-2, but only SHP-1 is required for CD300a inhibitory activity, as shown by siRNA knockdown and phosphatase-deficient DT40 cell lines. |
KIR-CD300a chimeric receptor in Jurkat T cells, siRNA knockdown of SHP-1/SHP-2/SHIP, DT40 phosphatase-deficient cell lines, calcium mobilization and proliferation assays |
BMC immunology |
High |
22537350
|
| 2012 |
CD300a selectively blocks TLR4/MyD88 and TLR9/MyD88-mediated pro-inflammatory signaling through SHP-1 activation, but does not block TLR3/TRIF-mediated signaling (unlike CD300f which requires combined SHP-1 and SHP-2); ITIM peptides of CD300a mimic this selective inhibition. |
THP-1/U937 stimulation with TLR ligands, luciferase NF-κB reporter assay, Western blotting, synthetic ITIM peptides, signaling inhibitors |
Immunology |
High |
22043923
|
| 2013 |
CD300a and CD300c both bind PS and additional unknown ligand(s) on tumor cells; blocking PS-CD300a interaction increases NK cell killing of tumor cells, demonstrating a tumor immune evasion mechanism. |
Anti-CD300a monoclonal antibody generation, NK cell cytotoxicity assays, antibody blocking experiments |
European journal of immunology |
Medium |
23640773
|
| 2013 |
CD300C delivers FcRγ-dependent activating signals in mast cells and monocytes; CD300A and CD300C differ in ligand recognition at residues F56-L57 (CD300A) vs. L63-R64 (CD300C), with PE binding more strongly to CD300A; CD300A expression is dominant over CD300C in PE recognition/signaling when co-expressed. |
Epitope-discriminating antibodies, reporter cell lines expressing CD300A/C-CD3ζ chimeras, GFP reporter assay, cytokine production assays, co-expression experiments |
Journal of biological chemistry |
High |
23372157
|
| 2013 |
CD300a mRNA and protein are upregulated following monocyte transendothelial migration; CD300a engagement reduces monocyte transmigration, siRNA knockdown increases transmigration rate, and activated CD300a causes F-actin cytoskeleton alterations and co-localizes with actin filaments. |
Transcriptional profiling, siRNA knockdown, anti-CD300a antibody treatment, migration assays, co-sedimentation with actin, immunofluorescence |
PloS one |
Medium |
24058511
|
| 2014 |
PPARβ/δ directly regulates CD300a transcription in macrophages; CD300a-deficient mice on high-fat diet develop chronic intestinal inflammation with prolonged IL-6 secretion from macrophages in response to LPS/TLR4-MyD88 signaling. |
CD300a KO mice, high-fat diet model, bone marrow transplantation, LPS stimulation, cytokine measurement |
Scientific reports |
Medium |
24958459
|
| 2015 |
CD300a binds DENV particles directly via PE (predominantly) and PS on the viral envelope, acting as an attachment factor that enhances DENV internalization through clathrin-mediated endocytosis; mutation of IgV domain residues critical for phospholipid binding abrogates CD300a-mediated viral enhancement. |
CD300a-Ig fusion binding to DENV, clathrin inhibitor experiments, site-directed mutagenesis of phospholipid-binding residues, viral infection assays, antibody inhibition in primary macrophages |
Journal of virology |
High |
26468529
|
| 2015 |
CD300a on inflammatory dendritic cells binds PS on apoptotic cells generated by alum adjuvant, promoting Th2 immune responses; CD300a-deficient mice show reduced eosinophilia, IgE, and airway hyperreactivity after alum+OVA immunization, and their DCs induce less IL-4 from CD4+ T cells. |
CD300a KO mice, allergic airway inflammation model, DC purification and co-culture, neutralizing antibody blockade |
Journal of immunology |
High |
25911756
|
| 2015 |
Pseudorabies virus US3 kinase triggers increased CD300a binding to the surface of infected cells via aminophospholipid ligands and group I p21-activated kinases (PAKs), thereby protecting virus-infected cells from NK cell-mediated lysis. |
Virus infection assays, NK cell cytotoxicity assays, PAK inhibitors, aminophospholipid manipulation |
Journal of virology |
Medium |
26581992
|
| 2021 |
CD300a on brain myeloid cells inhibits efferocytosis of apoptotic cells by blocking CD300b-DAP12 signaling; CD300a deficiency enhances efferocytosis, reduces DAMP release, and attenuates neurological deficit after ischemic stroke; anti-CD300a neutralizing antibody ameliorates stroke outcome. |
CD300a KO mice, MCAO model, efferocytosis assays, DAMP measurement, neutralizing antibody treatment, neurological scoring |
Science immunology |
High |
34652960
|
| 2021 |
CD300a on dendritic cells inhibits tumor-derived extracellular vesicle (TEV)-mediated TLR3-TRIF signaling for IFN-β production; TEV co-culture with DCs induces CD300a internalization and incorporation of EVs into endosomes where CD300a suppresses TLR3-TRIF-IFN-β-Treg axis, resulting in Treg accumulation and tumor growth. |
CD300a KO mice, B16 melanoma transplantation, EV pharmacological inhibition, DC-TEV co-culture, endosomal fractionation, tumor-infiltrating Treg cell counting |
eLife |
High |
34751648
|
| 2021 |
CD300a deficiency impairs neutrophil phagocytic ability during urinary tract infection despite increased accumulation at the infection site; UPEC's α-hemolysin toxin induces upregulation of CD300a ligands on infected bladder epithelial cells. |
CD300a KO mice, UPEC infection model, phagocytosis assays, bacterial burden measurement, α-hemolysin stimulation |
European journal of immunology |
Medium |
34268737
|
| 2021 |
CD300a agonistic antibody induces apoptosis of human neutrophils via caspase-8 cleavage, contributing to resolution of MSU crystal-induced articular inflammation; CD300a KO mice show persistent neutrophil influx and reduced efferocytosis after MSU injection. |
CD300a KO mice, MSU crystal gout model, agonistic antibody treatment, caspase-8 cleavage assay, efferocytosis quantification |
Immunology |
Medium |
34002852
|
| 2023 |
PPARβ/δ agonist GW0742 increases CD300a expression and SHP-1 phosphorylation in mast cells, reducing Syk phosphorylation and mast cell degranulation after germinal matrix hemorrhage; CD300a siRNA abolishes the protective effects. |
GMH rat model, siRNA knockdown of PPARβ/δ and CD300a, Western blotting for SHP-1 and Syk phosphorylation, mast cell degranulation markers |
Experimental neurology |
Medium |
37995951
|
| 2025 |
CD300a and CD300lf cooperate to inhibit mast cell activation; both receptors co-localize with PS externalized on the outer leaflet upon activation with polar formation; CD300lf additionally binds extracellular ceramide, providing stronger inhibition than PS binding alone; double KO mice show more severe anaphylaxis than single KOs. |
KO mouse bone marrow-derived mast cells (single and double KO), imaging and flow cytometry for receptor localization, passive systemic anaphylaxis model with temperature readout |
Journal of immunology |
High |
40073110
|
| 2024 |
CD300a specifically modulates PE-mediated phagocytic uptake by macrophages; CD300a and CD300b engage PE on apoptotic cells and extracellular vesicles through ITAM-containing adaptors and Syk kinase; CD300a expression curtails inflammatory responses of macrophages to PE particles containing LPS. |
Phagocytosis assays with PE-coated particles, CD300 family receptor knockdown/expression, Syk inhibitor experiments, LPS inflammatory response measurement |
bioRxivpreprint |
Medium |
bio_10.1101_2024.11.18.624161
|