Affinage

CD14

Monocyte differentiation antigen CD14 · UniProt P08571

Round 2 corrected
Length
375 aa
Mass
40.1 kDa
Annotated
2026-04-28
130 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD14 is a GPI-anchored pattern recognition co-receptor on monocytes, macrophages, and neutrophils that serves as the primary sensor and transfer molecule for bacterial lipopolysaccharide (LPS), peptidoglycan, lipoteichoic acid, lipopeptides, and apoptotic cell-derived phosphatidylinositides, coupling ligand capture to activation of distinct Toll-like receptor signaling pathways (PMID:1698311, PMID:7534618, PMID:35017647). The N-terminal leucine-rich region binds LPS–LBP complexes and transfers individual LPS molecules to TLR4/MD-2 via a defined LBP→CD14→TLR4-MD2 cascade, while presenting other microbial ligands to TLR2/TLR1 or TLR2/TLR6; CD14 additionally drives TLR4 endocytosis, thereby terminating MyD88-dependent signaling at the plasma membrane and initiating the TRAM-TRIF pathway from endosomes (PMID:28115037, PMID:27986454, PMID:10586073). A soluble form produced by hepatocytes as an IL-6-regulated acute-phase protein extends LPS sensing to CD14-low cells such as endothelial cells, while P2X7-dependent shedding of CD14 on extracellular vesicles modulates macrophage LPS responsiveness during sepsis (PMID:15034063, PMID:33135636). CD14 also mediates non-inflammatory phagocytosis of apoptotic cells by recognizing externalized phosphatidylinositides and phosphatidylserine, and participates in microglial recognition and phagocytosis of amyloid-β fibrils (PMID:9548256, PMID:35017647, PMID:15857927).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1988 High

    Establishing the membrane topology of CD14 resolved how a differentiation antigen lacking a transmembrane domain is surface-expressed: via a GPI linkage, with a smaller soluble isoform also produced.

    Evidence PI-phospholipase C cleavage, PNH patient monocytes lacking GPI-anchored proteins, cDNA cloning and SDS-PAGE

    PMID:2448876 PMID:2462937 PMID:3385210

    Open questions at the time
    • Three-dimensional structure of CD14 not yet determined
    • Mechanism of soluble CD14 generation (proteolytic vs. secretory) not resolved
  2. 1990 High

    Identifying CD14 as the receptor for LPS–LBP complexes established the molecular basis of monocyte endotoxin sensing, answering how picomolar LPS concentrations activate innate immunity.

    Evidence Direct LPS-LBP binding assays on monocytes, anti-CD14 mAb blockade of TNF-α production

    PMID:1698311

    Open questions at the time
    • Signal transduction mechanism downstream of a GPI-anchored protein unknown
    • Identity of transmembrane signaling partner not yet identified
  3. 1994 High

    Demonstrating that CD14 recognizes diverse Gram-positive and mycobacterial envelope components beyond LPS expanded it from an LPS receptor to a broad pattern recognition receptor.

    Evidence Cell activation assays with peptidoglycan, LTA, mycobacterial products; anti-CD14 blocking

    PMID:7534618 PMID:8798531

    Open questions at the time
    • Structural basis for multi-ligand binding not determined
    • Which downstream signaling receptors pair with CD14 for non-LPS ligands unknown
  4. 1995 High

    Mapping the LPS-binding determinants to four short motifs within the N-terminal 65 residues defined the functional domain architecture and showed that soluble CD14 fragments (152 aa) can reconstitute LPS signaling on CD14-deficient cells.

    Evidence Systematic deletion mutagenesis in CHO cells, NF-κB and LPS binding assays, reconstitution on PNH monocytes and endothelial cells

    PMID:7529231 PMID:7537790

    Open questions at the time
    • Atomic-resolution structure of CD14 N-terminal domain–LPS interaction not available
    • Determinants distinguishing membrane vs. soluble CD14 function not fully resolved
  5. 1996 High

    CD14 knockout mice proved CD14 is required for lethal endotoxin shock in vivo and unexpectedly revealed a role in bacterial dissemination, validating CD14 as a central innate immune gatekeeper.

    Evidence Gene-targeted CD14−/− mice challenged with LPS and live Gram-negative bacteria

    PMID:8612135

    Open questions at the time
    • How CD14 promotes bacterial dissemination mechanistically was not defined
    • Relative contributions of membrane vs. soluble CD14 in vivo not dissected
  6. 1998 High

    Discovering that CD14 mediates phagocytosis of apoptotic cells without provoking inflammation revealed a dual function — pathogen sensing and silent corpse clearance — through an overlapping but non-identical binding site.

    Evidence Anti-CD14 blocking antibodies, macrophage phagocytosis assays, cytokine measurement

    PMID:9548256

    Open questions at the time
    • Specific apoptotic cell ligand recognized by CD14 not identified at this point
    • Structural basis for anti-inflammatory vs. pro-inflammatory outcome unknown
  7. 1999 High

    Showing that CD14-dependent LAM signaling requires TLR2 while LPS signaling does not established the paradigm of CD14 as a shared ligand-capture receptor that routes different PAMPs to distinct TLR signaling complexes.

    Evidence CHO/CD14 transfection with TLR2, differential cytokine activation for LAM vs. LPS

    PMID:10586073

    Open questions at the time
    • Molecular mechanism by which CD14 hands off ligands to specific TLRs not defined
    • Role of co-receptors MD-1/MD-2 in this routing not addressed
  8. 2001 High

    UV cross-linking of LPS to TLR4/MD-2 only in the presence of CD14 demonstrated that CD14 is required for physical LPS transfer to TLR4-MD2, defining the tripartite receptor complex.

    Evidence HEK293 reconstitution, radio-iodinated ASD-LPS UV cross-linking, immunoprecipitation

    PMID:11274165

    Open questions at the time
    • Stoichiometry and kinetics of the transfer reaction not measured
    • Whether CD14 remains in the complex after LPS transfer or dissociates was unclear
  9. 2005 High

    Quantitative comparison of CD14+/+ and CD14−/− macrophages revealed that CD14 confers up to 150,000-fold sensitivity enhancement and structural discrimination among LPS variants, establishing CD14 as the specificity determinant of the LPS receptor.

    Evidence Dose-response TNF production with structurally diverse LPS variants in WT vs. CD14 KO macrophages

    PMID:16148141

    Open questions at the time
    • Structural basis for CD14's discriminatory capacity unresolved
    • Whether soluble CD14 can restore full discrimination in CD14−/− cells not tested
  10. 2015 High

    Identification of Gαi1/3–CD14–Gab1 complexes revealed a G-protein-coupled signaling axis linking CD14 to PI3K-Akt activation, TLR4 endocytosis, and IRF3-dependent interferon production.

    Evidence Co-immunoprecipitation, Gαi1/3 siRNA knockdown and KO mice, TLR4 endocytosis and IRF3 phosphorylation assays

    PMID:25825741

    Open questions at the time
    • Whether Gαi proteins bind CD14 directly or through an intermediary adapter not established
    • Structural basis of GPI-anchored CD14 coupling to heterotrimeric G proteins unknown
  11. 2017 High

    Reconstitution of the entire LBP→CD14→TLR4-MD2 LPS transfer cascade at single-molecule resolution defined the mechanism: LBP binds longitudinally to LPS micelles and catalytically loads single LPS monomers onto CD14, which then delivers them to TLR4-MD2.

    Evidence Negative-stain EM, single-molecule TIRF fluorescence, in vitro reconstituted cascade

    PMID:28115037

    Open questions at the time
    • High-resolution cryo-EM structure of CD14–LPS intermediate not available
    • Whether CD14 undergoes conformational change upon LPS binding is unresolved
  12. 2020 High

    Two advances resolved how CD14 controls the spatiotemporal switch between TLR4 signaling pathways and how macrophages regulate their own CD14 levels: CD14 drives TLR4 endocytosis to activate TRAM-TRIF while terminating TIRAP-MyD88 signaling, and P2X7-driven vesicular shedding of CD14 attenuates LPS responsiveness during sepsis.

    Evidence CD14 KO with TLR4 trafficking assays; P2X7 KO mice in cecal ligation-puncture sepsis model; extracellular vesicle analysis

    PMID:33057840 PMID:33135636

    Open questions at the time
    • Molecular trigger linking CD14 engagement to the endocytic machinery not identified
    • How P2X7-shed CD14-bearing vesicles function systemically — as decoys or as soluble CD14 equivalents — is not resolved
  13. 2022 High

    Identification of externalized phosphatidylinositides as the specific eat-me signal recognized by CD14 on apoptotic cells resolved a two-decade-old question about CD14's non-inflammatory ligand in efferocytosis.

    Evidence Unbiased proteomics, anti-PIP masking, CD14 KO phagocytes, in vivo irradiation model

    PMID:35017647

    Open questions at the time
    • Binding affinity and structural basis of CD14–PIP interaction not defined
    • Whether CD14-dependent efferocytosis uses the same N-terminal domain as LPS binding is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of CD14 bound to LPS or phosphatidylinositides, and the molecular mechanism by which GPI-anchored CD14 engages heterotrimeric G proteins and the endocytic machinery to drive TLR4 internalization, remain undefined.
  • No atomic-resolution structure of CD14 in complex with any ligand
  • Mechanism coupling GPI-anchored CD14 to Gαi and endocytic machinery unresolved
  • Relative in vivo contributions of membrane-anchored vs. soluble vs. vesicular CD14 in sepsis and efferocytosis not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 8 GO:0038024 cargo receptor activity 4 GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 7 GO:0005576 extracellular region 4 GO:0005768 endosome 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-168256 Immune System 14 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 2
Partners
GAB1GNAI1GNAI3LBPMD2P2RX7TLR2TLR4
Complex memberships
LBP/CD14/LPSTLR2/CD14TLR4/MD-2/CD14

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 CD14 is anchored to the monocyte plasma membrane via a glycosylphosphatidylinositol (GPI) linkage, as demonstrated by removal of surface CD14 with PI-phospholipase C and absence of CD14 on monocytes from a paroxysmal nocturnal hemoglobinuria patient lacking GPI-anchored proteins; a smaller soluble form lacking the GPI anchor is also secreted. PI-phospholipase C treatment, immunofluorescence of PNH patient monocytes, biosynthetic labeling, SDS-PAGE Journal of immunology High 2462937 3385210
1988 CD14 maps to chromosome 5q31 in a region encoding myeloid growth factors and receptors, and encodes a myelomonocytic differentiation antigen expressed on monocytes, macrophages, and activated granulocytes. cDNA cloning, genomic mapping, flow cytometry Science High 2448876
1989 CD14 cDNA encodes a protein lacking a transmembrane domain, confirmed to be GPI-anchored by PI-PLC release and absence on PNH monocytes; a single mRNA species is abundantly expressed in monocytes and is induced during myeloid differentiation. cDNA library expression cloning, RNA/DNA blot, PI-PLC treatment, PNH patient cells Blood High 2462937
1990 CD14 functions as a receptor for complexes of LPS and LPS-binding protein (LBP): LPS-LBP complexes bind to CD14 on monocyte surfaces, and anti-CD14 monoclonal antibody blockade prevents LPS/LBP-induced TNF-α synthesis. Binding assays with LPS-LBP complexes, anti-CD14 mAb blocking, TNF-α measurement in whole blood Science High 1698311
1993 Transgenic mice expressing human CD14 on monocytes, neutrophils, and lymphocytes are hypersensitive to LPS-induced endotoxin shock, establishing CD14 as a primary mediator of LPS lethality in vivo. Transgenic mouse generation, LPS challenge survival assay, flow cytometry Proceedings of the National Academy of Sciences High 7681594
1993 CD14 on neutrophils in whole blood mediates LPS-induced upregulation of CR3 (CD11b/CD18); anti-CD14 antibodies inhibit this CR3 upregulation, indicating CD14 is the primary neutrophil sensor for LPS. Flow cytometry in whole blood, anti-CD14 mAb inhibition Journal of leukocyte biology Medium 7684764
1994 CD14 acts as a pattern recognition receptor for diverse bacterial envelope components from Gram-negative and Gram-positive bacteria and mycobacteria, initiating cell activation beyond just LPS. Cell activation assays with diverse bacterial ligands, anti-CD14 mAb blocking Immunity High 7534618
1995 The N-terminal 65 amino acids of CD14, specifically four small regions (including AVEVE, DDED, PQPD, DPRQY), are critical for serum-dependent LPS binding and NF-κB activation; deletion mutants in this region largely abolish LPS receptor function. Deletion mutagenesis in CHO cells, LPS binding assays, NF-κB activation Journal of Biological Chemistry High 7529231
1995 Soluble CD14 (recombinant, truncated to N-terminal 152 amino acids) enables LPS activation of CD14-deficient PNH monocytes and endothelial cells, demonstrating that soluble CD14 in serum can substitute for membrane CD14 in LPS signaling. Recombinant soluble CD14, tissue factor and TNF-α assays in CD14-deficient PNH cells and endothelial cells Journal of laboratory and clinical medicine High 7537790
1996 CD14 is a functional cell-activating receptor for bacterial peptidoglycan; the N-terminal 151 amino acids are sufficient for full responsiveness, and similar but not identical sequences within the N-terminal 65 amino acids are critical for responses to both peptidoglycan and LPS. CD14 transfection in 70Z/3 cells, NF-κB activation, IκB-α degradation, IgM expression, deletion mutagenesis Journal of Biological Chemistry High 8798531
1996 CD14-deficient mice generated by gene targeting are highly resistant to endotoxin shock from live Gram-negative bacteria or LPS, and also show dramatically reduced bacteremia, revealing an unexpected role for CD14 in bacterial dissemination. Gene targeting in ES cells, LPS/bacterial challenge survival, bacteremia measurement Immunity High 8612135
1998 CD14 mediates recognition and phagocytosis of apoptotic cells by human macrophages; this interaction depends on a region of CD14 that overlaps with the LPS-binding site, yet unlike LPS, apoptotic cells do not provoke pro-inflammatory cytokine release. Anti-CD14 blocking antibodies, phagocytosis assays, cytokine measurement Nature High 9548256
1998 CD14 internalizes via macropinocytosis (not clathrin-coated pits or caveolae): CD14 localizes to microfilament-enriched ruffles and large macropinosomes, LPS co-localizes with CD14 in endosomal compartments, and cytochalasin D blocks internalization but not LPS-dependent cell activation, dissociating endocytosis from signaling. Electron microscopy, sucrose density gradient fractionation, confocal microscopy, cytochalasin D inhibition, radiolabeled LPS tracking in GPI and transmembrane CD14 THP-1 transfectants Journal of Biological Chemistry High 9685378
1998 Both GPI-anchored and transmembrane forms of CD14 support LPS-mediated NF-κB activation and cytokine production similarly, indicating GPI anchoring is not required for LPS signaling; however, only GPI-anchored CD14 mediates rapid calcium mobilization upon antibody cross-linking, implicating phospholipase C and protein tyrosine kinases. THP-1 cells stably expressing GPI or transmembrane CD14, NF-κB activation, cytokine ELISA, calcium mobilization assays, pharmacological inhibitors, Triton X-100 fractionation Infection and immunity High 9488411
1999 Distinct CD14 ligands LAM and LPS utilize different TLR proteins for intracellular signaling: CHO/CD14 cells acquire LAM responsiveness only when also engineered to express functional TLR2, while LPS signaling does not require TLR2, establishing a paradigm where a common binding receptor (CD14) pairs with distinct signal-transducing receptors. CHO transfection with CD14 and TLR2, cytokine activation assays, TLR2 overexpression in macrophages Journal of immunology High 10586073
2000 Membrane and soluble forms of CD14 have different structural determinants for LPS receptor function: deletions that abolish LPS binding in membrane CD14 may not affect binding in soluble CD14, yet all five tested deletions ablated soluble CD14 receptor function whereas only two completely destroyed membrane CD14 receptor function. Deletion mutants of CD14 expressed in CHO cells, LPS binding assays, soluble CD14-dependent cellular activation assays Journal of Biological Chemistry High 10652298
2001 LPS cross-links specifically to TLR4 and MD-2 only when CD14 is co-expressed, establishing that LPS is in close proximity to all three members of the tripartite receptor complex (CD14, TLR4, MD-2) and that CD14 is required for LPS transfer to TLR4/MD-2. Transient transfection in HEK293 cells, UV cross-linking with radio-iodinated ASD-LPS, immunoprecipitation Journal of Biological Chemistry High 11274165
2001 Following LPS stimulation, CD14 forms an activation cluster with heat-shock proteins Hsp70 and Hsp90, chemokine receptor CXCR4, and GDF5, as identified by affinity chromatography and confirmed by FRET, suggesting these proteins serve as the transmembrane signaling components downstream of CD14. Affinity chromatography, peptide mass fingerprinting, fluorescence resonance energy transfer (FRET) Nature immunology Medium 11276205
2002 LPS traffics rapidly to and from the Golgi apparatus with the TLR4-MD-2-CD14 complex; LPS follows CD14-dependent trafficking pathways in CD14-positive cells, but Golgi-associated TLR4 expression disrupted by brefeldin A does not prevent LPS signaling, indicating signaling is initiated at the plasma membrane. Fluorescent TLR4 expression, confocal microscopy of LPS trafficking, brefeldin A inhibition, MyD88 translocation assays, cross-linking signaling assays Journal of Biological Chemistry High 12324469
2003 Human CMV virions are recognized by TLR2 and CD14 to trigger NF-κB-dependent inflammatory cytokine production; both receptors are required for CMV-induced innate immune activation. TLR2/CD14 antibody blocking, dominant-negative TLR constructs, NF-κB reporter assays, cytokine measurement Journal of virology High 12663765
2003 Lipoteichoic acid from S. pneumoniae and S. aureus activates immune cells via LBP, CD14, and TLR2, but not TLR4/MD-2; LBP catalytically transfers LTA to CD14, and TLR2 transfection in HEK293/CD14 and CHO cells confers LTA responsiveness. PhastGel native gel electrophoresis, HEK293/CHO transfection, cytokine induction assays, anti-CD14/anti-LBP blocking Journal of Biological Chemistry High 12594207
2003 CD14 interacts directly with Alzheimer's amyloid-β peptide (Aβ42) fibrils and mediates microglial activation; anti-CD14 antibodies and CD14 genetic deficiency significantly reduce amyloid-induced microglial activation and toxicity. FRET/FLIM, antibody neutralization, CD14-knockout cell experiments, flow cytometry, confocal microscopy FASEB journal Medium 14597556
2004 Soluble CD14 is produced by the liver as a type 2 acute-phase protein regulated by IL-6: IL-6 stimulates CD14 mRNA and protein production in HepG2 cells and primary hepatocytes, and CD14 mRNA induction during acute-phase response is abolished in IL-6-knockout mice. ELISA, real-time PCR, HepG2 cell stimulation, IL-6 knockout mouse model with turpentine injection Journal of immunology High 15034063
2005 CD14 directly interacts with Aβ42 at nanometer range (confirmed by FRET/FLIM) and mediates phagocytosis of exogenous Aβ42 by primary microglia at sub-inflammatory concentrations in a CD14-dependent manner; CD14 knockout cells fail to internalize Aβ42. Flow cytometry, confocal microscopy, two-photon FLIM-FRET, CD14-deficient microglial cells, phagocytosis assay Brain High 15857927
2005 CD14 determines ligand specificity of the LPS receptor complex: CD14+/+ macrophages show exquisite sensitivity (up to 150,000-fold greater than CD14-/- cells) and structural discrimination between smooth LPS and partial structures, whereas CD14-/- macrophages cannot distinguish LPS structural variants. Comparison of CD14+/+ and CD14-/- macrophage responses to structurally diverse LPS variants, TNF production assays Journal of immunology High 16148141
2005 Lipopeptide binding to CD14 is the first step in LP recognition; after Pam3CSK4 binding, CD14 and the lipopeptide associate with TLR2/TLR1, and TLR2 is recruited to a low-mobility signaling complex. CD14 enables lipopeptide binding while TLR2 is required for signaling. FRET and FRAP imaging, flow cytometry, confocal microscopy with FLAG-labeled lipopeptide European journal of immunology High 15714590
2005 Ethanol disrupts LPS-induced lipid raft clustering by altering CD14 partition into lipid rafts; EtOH interferes with IRAK-1 activation and suppresses TLR4-mediated TNF-α production in a manner additive with chemical lipid raft disruptors. Cell fractionation, TNF-α ELISA, IRAK-1 activation assay, methyl-β-cyclodextrin/nystatin comparison Biochemical and biophysical research communications Medium 15896296
2012 LPS causes CD14 membrane expression and colocalization with TLR-4 in intestinal enterocytes, and this TLR-4-dependent CD14 upregulation mediates LPS-induced increase in intestinal tight junction permeability both in vitro and in vivo. Caco-2 monolayer transepithelial resistance, mouse intestinal perfusion, TLR-4 KO comparison, confocal colocalization American Journal of Pathology High 23201091
2015 Gαi1 and Gαi3 form complexes with CD14 and Gab1 in response to LPS, which are required for PI3K-Akt signaling activation; Gαi1/3 deficiency decreases TLR4 endocytosis, reduces IRF3 phosphorylation, causes an M2-like macrophage phenotype with suppressed pro-inflammatory cytokine production, and leads to LPS tolerance in vivo. Co-immunoprecipitation, Gαi1/3 siRNA knockdown in BMDMs, Gαi1/3 KO mice, cytokine ELISA, TLR4 endocytosis assay, IRF3 phosphorylation PNAS High 25825741
2016 CD14 is required for TLR4 endocytosis and thereby for the TRAM-TRIF-dependent signaling pathway activated from early endosomes; without CD14, TLR4 cannot be internalized efficiently, abrogating IFN-β production downstream of TRIF while MyD88-dependent signaling at the plasma membrane is less affected. Review synthesizing CD14 KO, endocytosis assays, TLR4 trafficking studies Immunity High 27986454
2017 A single LPS molecule bound to CD14 is transferred to TLR4-MD2 in a TLR4-dependent manner; LBP binds longitudinally to LPS micelles and catalyzes multi-round LPS transfer to CD14 via electrostatic interactions; CD14 then delivers single LPS molecules to TLR4-MD2 through a defined cascade involving LBP/LPS micelle → CD14/LBP/LPS ternary → CD14-LPS-TLR4-MD2 intermediates. Negative-stain electron microscopy, single-molecule TIRF fluorescence analysis, reconstituted in vitro LPS transfer cascade BMB reports High 28115037
2020 P2X7 receptor activation induces release of CD14 from macrophages via extracellular vesicles, reducing plasma membrane CD14 and functionally attenuating LPS-induced (but not monophosphoryl lipid A-induced) pro-inflammatory cytokine production; P2X7 activity is required during murine sepsis to maintain elevated circulating CD14 levels and control bacterial load. Extracellular vesicle isolation, flow cytometry, P2X7 KO mice, cecal ligation/puncture sepsis model, cytokine measurement eLife High 33135636
2020 CD14 governs TLR4 endocytosis and thus the spatiotemporal control of LPS-induced signaling: CD14-driven internalization of TLR4 terminates TIRAP/MyD88-dependent signaling at the plasma membrane while activating the TRAM/TRIF-dependent pathway from early endosomes; subsequent endo-lysosomal trafficking of TLR4 determines the duration and magnitude of TRIF-dependent responses. Review synthesizing CD14 KO, TLR4 endocytosis, TRIF/MyD88 pathway activation assays from multiple studies Cellular and molecular life sciences High 33057840
2022 Externalized phosphatidylinositides (PIPs) on apoptotic cell surfaces are eat-me signals recognized by CD14; masking exofacial PIPs or CD14 knockout in phagocytes blocks phagocytosis of apoptotic cells, and CD14-deficient mice accumulate PIP+ apoptotic cells in tissues. Unbiased proteomics, anti-PI(3,4,5)P3 antibody/PH-domain probes, CD14 KO phagocytes, in vivo irradiation model, flow cytometry Cell death and differentiation High 35017647
1999 CD14 is expressed on Kupffer cells and is functional: LPS induces CD14-dependent intracellular calcium rises and TNF-α mRNA in collagenase-isolated Kupffer cells; Pronase treatment removes surface CD14 and abolishes LPS responses, while PI-PLC cleavage of CD14 blunts calcium signaling. Western blotting, RT-PCR, intracellular calcium measurement, TNF-α mRNA, Pronase vs. collagenase isolation comparison, PI-PLC treatment American Journal of Physiology Medium 10070034
2009 Chicken CD14, unlike its mammalian ortholog, is a transmembrane protein rather than GPI-anchored: it contains a 23-aa transmembrane segment and a cytoplasmic tail, and PI-PLC treatment does not remove chicken CD14 from the cell surface in transfected COS-7 cells. RT-PCR cloning, COS-7 transfection with FLAG-tagged constructs, PI-PLC treatment, flow cytometry Developmental and comparative immunology High 18761368

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science (New York, N.Y.) 3457 1698311
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1990 Structure and function of lipopolysaccharide binding protein. Science (New York, N.Y.) 1440 2402637
2020 TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cellular and molecular life sciences : CMLS 1072 33057840
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2010 Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 969 20832340
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1988 The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. Journal of immunology (Baltimore, Md. : 1950) 583 3385210
1996 Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. Immunity 580 8612135
2002 Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster. Trends in immunology 563 12072369
1994 CD14 is a pattern recognition receptor. Immunity 559 7534618
2012 Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. The American journal of pathology 544 23201091
2008 Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. The Journal of clinical investigation 536 18497880
1998 Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 529 9548256
2003 Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. Journal of virology 520 12663765
2001 Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. transfer from CD14 to TLR4 and MD-2. The Journal of biological chemistry 483 11274165
2003 Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. The Journal of biological chemistry 476 12594207
2011 SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset. Blood 455 21803849
2012 CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. Journal of the American College of Cardiology 452 22999728
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2002 Toll receptors, CD14, and macrophage activation and deactivation by LPS. Microbes and infection 428 12106783
2002 Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections. The Journal of infectious diseases 426 12404174
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2006 Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. The Journal of biological chemistry 369 16880211
2002 Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction. The Journal of biological chemistry 352 12324469
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2016 Reconstruction of LPS Transfer Cascade Reveals Structural Determinants within LBP, CD14, and TLR4-MD2 for Efficient LPS Recognition and Transfer. Immunity 340 27986454
1998 LPS-binding proteins and receptors. Journal of leukocyte biology 339 9665271
2001 A CD14-independent LPS receptor cluster. Nature immunology 326 11276205
1988 The CD14 monocyte differentiation antigen maps to a region encoding growth factors and receptors. Science (New York, N.Y.) 326 2448876
2004 Cell surface-associated elongation factor Tu mediates the attachment of Lactobacillus johnsonii NCC533 (La1) to human intestinal cells and mucins. Infection and immunity 302 15039339
1999 The CD14 ligands lipoarabinomannan and lipopolysaccharide differ in their requirement for Toll-like receptors. Journal of immunology (Baltimore, Md. : 1950) 299 10586073
2005 LPS receptor (CD14): a receptor for phagocytosis of Alzheimer's amyloid peptide. Brain : a journal of neurology 290 15857927
2010 Population alterations of L-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14⁻/CD15+/CD33+ myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer. Journal of cancer research and clinical oncology 269 19572148
2011 Two unique human decidual macrophage populations. Journal of immunology (Baltimore, Md. : 1950) 268 21257965
1989 Monocyte antigen CD14 is a phospholipid anchored membrane protein. Blood 265 2462937
2003 The LPS receptor (CD14) links innate immunity with Alzheimer's disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 247 14597556
2013 Role of CD14 in host protection against infections and in metabolism regulation. Frontiers in cellular and infection microbiology 213 23898465
2004 CD14 is an acute-phase protein. Journal of immunology (Baltimore, Md. : 1950) 213 15034063
2001 Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells. Journal of immunology (Baltimore, Md. : 1950) 206 11544322
2001 Association of a promoter polymorphism of the CD14 gene and atopy. American journal of respiratory and critical care medicine 202 11282774
1996 Human monocyte CD14 is upregulated by lipopolysaccharide. Infection and immunity 195 8613389
1993 Transgenic mice expressing human CD14 are hypersensitive to lipopolysaccharide. Proceedings of the National Academy of Sciences of the United States of America 186 7681594
1999 Human osteoclasts derive from CD14-positive monocytes. British journal of haematology 183 10444181
1996 CD14 is a cell-activating receptor for bacterial peptidoglycan. The Journal of biological chemistry 174 8798531
2010 Senescent CD14+CD16+ monocytes exhibit proinflammatory and proatherosclerotic activity. Journal of immunology (Baltimore, Md. : 1950) 158 21191073
2000 Selective mobilization of CD14(+)CD16(+) monocytes by exercise. American journal of physiology. Cell physiology 155 10942707
2010 Experimental human cytomegalovirus latency in CD14+ monocytes. Proceedings of the National Academy of Sciences of the United States of America 146 21041645
2000 CD14, new aspects of ligand and signal diversity. Microbes and infection 134 10758406
2005 Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1. European journal of immunology 120 15714590
1996 Antibodies against CD14 protect primates from endotoxin-induced shock. The Journal of clinical investigation 117 8833900
2017 Dynamic lipopolysaccharide transfer cascade to TLR4/MD2 complex via LBP and CD14. BMB reports 105 28115037
2001 CD14 is expressed and released as soluble CD14 by human intestinal epithelial cells in vitro: lipopolysaccharide activation of epithelial cells revisited. Infection and immunity 100 11349042
2005 Activation of peripheral blood CD14+ monocytes occurs in diabetes. Diabetes 97 16123369
2014 Expansion and preferential activation of the CD14(+)CD16(+) monocyte subset during multiple sclerosis. Immunology and cell biology 93 24638064
2007 CD14, endotoxin, and asthma risk: actions and interactions. Proceedings of the American Thoracic Society 93 17607003
2023 Role of CD14 in human disease. Immunology 92 36840585
1998 CD14-dependent endotoxin internalization via a macropinocytic pathway. The Journal of biological chemistry 92 9685378
1995 A region of human CD14 required for lipopolysaccharide binding. The Journal of biological chemistry 91 7529231
2006 Differential healing activities of CD34+ and CD14+ endothelial cell progenitors. Arteriosclerosis, thrombosis, and vascular biology 84 16410458
2004 Antitumor response of CD14+/CD16+ monocyte subpopulation. Experimental hematology 79 15308326
2001 Synthesis and surface expression of CD14 by human endothelial cells. Infection and immunity 76 11119540
1998 CD11/CD18 and CD14 share a common lipid A signaling pathway. Journal of immunology (Baltimore, Md. : 1950) 75 9820516
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