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Gene Review

CD14  -  CD14 molecule

Homo sapiens

Synonyms: Monocyte differentiation antigen CD14, Myeloid cell-specific leucine-rich glycoprotein
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Disease relevance of CD14

  • This binding activity was enhanced by agonists that upregulated CD14 expression and may serve in the clearance of Gram-negative bacteria opsonized with LBP [1].
  • Lipopolysaccharide-binding protein (LBP) is a recently identified hepatic secretory protein potentially involved in the pathogenesis of sepsis, capable of binding the bacterial cell wall product endotoxin and directing it to its cellular receptor, CD14 [2].
  • Culture-activated HSCs and HSCs isolated from patients with hepatitis C virus-induced cirrhosis express LPS-associated signaling molecules, including CD14, toll-like receptor (TLR) 4, and MD2 [3].
  • Cotransfection of type 2 and human CD14 or MD-2 into human embryonic kidney 293 cells allowed the response to Escherichia coli lipopolysaccharide (LPS), whereas type 1 did not signal LPS or any other microbial components tested [4].
  • Lastly, HIV-1 derived from the lung contains CD14, suggesting that they were produced in AM [5].
  • The frequencies of both the CC genotype and the C allele of CD14 -550 C/T were significantly higher in children with RSV bronchiolitis than in the control subjects [6].

Psychiatry related information on CD14

  • CD14 receptor polymorphism and Alzheimer's disease risk [7].
  • METHODS: CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls [8].
  • Means (SD) for CD14/CD16 in HIV-negative controls and in AIDS non-dementia and AIDS dementia patients were 6.5% (4), 16% (13), and 37% (21), respectively (p = 0.008 between the two groups of patients) [9].
  • Gene by environment interaction: the -159C/T polymorphism in the promoter region of the CD14 gene modifies the effect of alcohol consumption on serum IgE levels [10].
  • The genetic determination of the defense mechanisms in CD appears to be associated with the polymorphism of the Hsp70-2 gene rather than that of the CD14 or IL-10 genes [11].

High impact information on CD14

  • We also review the evidence supporting a model for a functional LPS receptor of myeloid cells, which is multimeric, comprised of GPI-anchored CD14 and a presently unidentified transmembrane protein that together bind LPS and initiate cell activation via kinase cascades [12].
  • These findings indicate that CD14 is a co-receptor for HSP70-mediated signaling in human monocytes and are indicative of an previously unrecognized function for HSP70 as an extracellular protein with regulatory effects on human monocytes, having a dual role as chaperone and cytokine [13].
  • Here we show that Toll-like receptor 2 (TLR2) is a signalling receptor that is activated by LPS in a response that depends on LPS-binding protein and is enhanced by CD14 [14].
  • Overstimulation of CD14 by LPS can cause the often fatal toxic-shock syndrome [15].
  • Here we show that the glycosylphosphatidylinositol-linked plasma-membrane glycoprotein CD14 on the surface of human macrophages is important for the recognition and clearance of apoptotic cells [15].

Chemical compound and disease context of CD14


Biological context of CD14


Anatomical context of CD14


Associations of CD14 with chemical compounds

  • Cells of the THP-1 human monocyte-macrophage cell line were exposed to 1,25 dihydroxyvitamin D3 to induce adherence to plastic and expression of CD14, a binding receptor for LPS complexed with LPS-binding protein (LBP) [22].
  • Mø2s were shown to use CD14 to tether apoptotic cells, whereas recognition of phosphatidylserine (PS) contributed to uptake of early apoptotic cells [27].
  • Acivicin caused a monocytoid differentiation of the cells as manifest by diminished cell growth, morphologic maturation of the cells, increased ability to generate hydrogen peroxide in response to acute treatment with phorbol myristate acetate, and increased expression of nonspecific esterase and the surface antigens CD14 and CD11b [28].
  • Basal CD14 and CD11b expression were slightly reduced by DEX and PTX, but neither drug modified the acivicin-induced increases [28].
  • Flow cytometry using fluoresceinated LPS showed that chenodeoxycholate does not interact with the CD14 receptor, thus excluding the possibility of an interference with the LPS uptake by monocytes [29].
  • A functional role is observed for the first disulfide bond because the C6A substitution severely reduces the ability of CD14 to confer lipopolysaccharide responsiveness to U373 cells [30].

Physical interactions of CD14

  • These results indicate that the CD14 region spanning amino acids 57-64 is critical for interacting with TLR2 and enhancing TLR2-mediated peptidoglycan signaling [31].
  • Rapid recycling of TLR4/CD14/MD-2 complexes between the Golgi and the plasma membrane was a prominent phenomenon [32].
  • The serum protein lipopolysaccharide-binding protein (LBP) binds to the lipid A component of bacterial endotoxin and facilitates its delivery to the CD14 antigen on the macrophage, where inflammatory cytokines are released and a cascade of host mediators is initiated [33].
  • Lipopolysaccharide-coated erythrocytes activate human neutrophils via CD14 while subsequent binding is through CD11b/CD18 [34].
  • TNF activation restored ELPS binding in CD14-blocked cells but not in cells in which CR3 was blocked [34].

Regulatory relationships of CD14

  • Coexpression of CD14 synergistically enhanced LPS signal transmission through TLR2 [35].
  • However, the ability of LBP and CD14 to efficiently promote TLR4-dependent cell activation by membrane-associated endotoxin has not been studied extensively [36].
  • Interleukin 4 down-regulates the expression of CD14 in normal human monocytes [37].
  • The addition of IL-10 at the initiation of culture resulted in the generation of macrophage-like cells with expressing high levels of CD14 and decreased levels of CD1a and CD1c [38].
  • Treatment of T24 and 5637 cells with phosphatidylinositol-specific phospholipase C to eliminate CD14 from the cell surface dramatically suppressed the induction of IL-8 [39].

Other interactions of CD14

  • Transfection of either human or murine TLR9 conferred responsiveness in a CD14- and MD2-independent manner, yet required species-specific CpG-DNA motifs for initiation of the Toll/IL-1R signal pathway via MyD88 [40].
  • LPS-binding protein (LBP) and soluble CD14 increased the sensitivity of TLR4-expressing epithelial cells to LPS but were not able to mediate LPS activation of these cells in the absence of soluble MD-2 [41].
  • In contrast, maturation of cells into the monocytic pathway was indicated by the acquisition of LZ followed by MPO and CD14 [42].
  • Comparison of PBDCs versus BMDCs showed higher surface expression of HLA-DR (P =.01), CD86 (P =. 0003), and CD14 (P =.04) on PBDCs [43].
  • Our data suggest that innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic complications in the course of infectious diseases brought about by the clinically most important Gram-positive pathogens [44].

Analytical, diagnostic and therapeutic context of CD14


  1. Activation of the adhesive capacity of CR3 on neutrophils by endotoxin: dependence on lipopolysaccharide binding protein and CD14. Wright, S.D., Ramos, R.A., Hermanowski-Vosatka, A., Rockwell, P., Detmers, P.A. J. Exp. Med. (1991) [Pubmed]
  2. The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins. Schumann, R.R., Kirschning, C.J., Unbehaun, A., Aberle, H.P., Knope, H.P., Lamping, N., Ulevitch, R.J., Herrmann, F. Mol. Cell. Biol. (1996) [Pubmed]
  3. Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Paik, Y.H., Schwabe, R.F., Bataller, R., Russo, M.P., Jobin, C., Brenner, D.A. Hepatology (2003) [Pubmed]
  4. Molecular cloning and functional characterization of chicken toll-like receptors. A single chicken toll covers multiple molecular patterns. Fukui, A., Inoue, N., Matsumoto, M., Nomura, M., Yamada, K., Matsuda, Y., Toyoshima, K., Seya, T. J. Biol. Chem. (2001) [Pubmed]
  5. Mycobacterium tuberculosis-induced CXCR4 and chemokine expression leads to preferential X4 HIV-1 replication in human macrophages. Hoshino, Y., Tse, D.B., Rochford, G., Prabhakar, S., Hoshino, S., Chitkara, N., Kuwabara, K., Ching, E., Raju, B., Gold, J.A., Borkowsky, W., Rom, W.N., Pine, R., Weiden, M. J. Immunol. (2004) [Pubmed]
  6. CD14 -550 C/T, which is related to the serum level of soluble CD14, is associated with the development of respiratory syncytial virus bronchiolitis in the Japanese population. Inoue, Y., Shimojo, N., Suzuki, Y., Campos Alberto, E.J., Yamaide, A., Suzuki, S., Arima, T., Matsuura, T., Tomiita, M., Aoyagi, M., Hoshioka, A., Honda, A., Hata, A., Kohno, Y. J. Infect. Dis. (2007) [Pubmed]
  7. CD14 receptor polymorphism and Alzheimer's disease risk. Combarros, O., Infante, J., Rodríguez, E., Llorca, J., Peña, N., Fernández-Viadero, C., Berciano, J. Neurosci. Lett. (2005) [Pubmed]
  8. Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection. Meiler, C., Muhlbauer, M., Johann, M., Hartmann, A., Schnabl, B., Wodarz, N., Schmitz, G., Scholmerich, J., Hellerbrand, C. World J. Gastroenterol. (2005) [Pubmed]
  9. Unique monocyte subset in patients with AIDS dementia. Pulliam, L., Gascon, R., Stubblebine, M., McGuire, D., McGrath, M.S. Lancet (1997) [Pubmed]
  10. Gene by environment interaction: the -159C/T polymorphism in the promoter region of the CD14 gene modifies the effect of alcohol consumption on serum IgE levels. Campos, J., Gude, F., Quinteiro, C., Vidal, C., Gonzalez-Quintela, A. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  11. Polymorphism of the heat-shock protein gene Hsp70-2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn's disease. Klausz, G., Molnár, T., Nagy, F., Gyulai, Z., Boda, K., Lonovics, J., Mándi, Y. Scand. J. Gastroenterol. (2005) [Pubmed]
  12. Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Ulevitch, R.J., Tobias, P.S. Annu. Rev. Immunol. (1995) [Pubmed]
  13. HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Asea, A., Kraeft, S.K., Kurt-Jones, E.A., Stevenson, M.A., Chen, L.B., Finberg, R.W., Koo, G.C., Calderwood, S.K. Nat. Med. (2000) [Pubmed]
  14. Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Yang, R.B., Mark, M.R., Gray, A., Huang, A., Xie, M.H., Zhang, M., Goddard, A., Wood, W.I., Gurney, A.L., Godowski, P.J. Nature (1998) [Pubmed]
  15. Human CD14 mediates recognition and phagocytosis of apoptotic cells. Devitt, A., Moffatt, O.D., Raykundalia, C., Capra, J.D., Simmons, D.L., Gregory, C.D. Nature (1998) [Pubmed]
  16. A novel synthetic acyclic lipid A-like agonist activates cells via the lipopolysaccharide/toll-like receptor 4 signaling pathway. Lien, E., Chow, J.C., Hawkins, L.D., McGuinness, P.D., Miyake, K., Espevik, T., Gusovsky, F., Golenbock, D.T. J. Biol. Chem. (2001) [Pubmed]
  17. Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness. Sugawara, S., Nemoto, E., Tada, H., Miyake, K., Imamura, T., Takada, H. J. Immunol. (2000) [Pubmed]
  18. The polysaccharide portion plays an indispensable role in Salmonella lipopolysaccharide-induced activation of NF-kappaB through human toll-like receptor 4. Muroi, M., Tanamoto, K. Infect. Immun. (2002) [Pubmed]
  19. Lipopolysaccharide-mimetic activities of a Toll-like receptor 2-stimulatory substance(s) in enterobacterial lipopolysaccharide preparations. Muroi, M., Ohnishi, T., Azumi-Mayuzumi, S., Tanamoto, K. Infect. Immun. (2003) [Pubmed]
  20. Induction of tumor necrosis factor production from monocytes stimulated with mannuronic acid polymers and involvement of lipopolysaccharide-binding protein, CD14, and bactericidal/permeability-increasing factor. Jahr, T.G., Ryan, L., Sundan, A., Lichenstein, H.S., Skjåk-Braek, G., Espevik, T. Infect. Immun. (1997) [Pubmed]
  21. Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. Pajkrt, D., Doran, J.E., Koster, F., Lerch, P.G., Arnet, B., van der Poll, T., ten Cate, J.W., van Deventer, S.J. J. Exp. Med. (1996) [Pubmed]
  22. Lipopolysaccharide (LPS) partial structures inhibit responses to LPS in a human macrophage cell line without inhibiting LPS uptake by a CD14-mediated pathway. Kitchens, R.L., Ulevitch, R.J., Munford, R.S. J. Exp. Med. (1992) [Pubmed]
  23. Lipopolysaccharide binding protein and CD14 interaction induces tumor necrosis factor-alpha generation and neutrophil sequestration in lungs after intratracheal endotoxin. Ishii, Y., Wang, Y., Haziot, A., del Vecchio, P.J., Goyert, S.M., Malik, A.B. Circ. Res. (1993) [Pubmed]
  24. Potentiation of lipopolysaccharide-induced tumor necrosis factor-alpha expression by 1,25-dihydroxyvitamin D3. Prehn, J.L., Fagan, D.L., Jordan, S.C., Adams, J.S. Blood (1992) [Pubmed]
  25. Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Werts, C., Tapping, R.I., Mathison, J.C., Chuang, T.H., Kravchenko, V., Saint Girons, I., Haake, D.A., Godowski, P.J., Hayashi, F., Ozinsky, A., Underhill, D.M., Kirschning, C.J., Wagner, H., Aderem, A., Tobias, P.S., Ulevitch, R.J. Nat. Immunol. (2001) [Pubmed]
  26. Cytokines in chronic inflammatory arthritis. IV. Granulocyte/macrophage colony-stimulating factor-mediated induction of class II MHC antigen on human monocytes: a possible role in rheumatoid arthritis. Alvaro-Gracia, J.M., Zvaifler, N.J., Firestein, G.S. J. Exp. Med. (1989) [Pubmed]
  27. IL-10-producing macrophages preferentially clear early apoptotic cells. Xu, W., Roos, A., Schlagwein, N., Woltman, A.M., Daha, M.R., van Kooten, C. Blood (2006) [Pubmed]
  28. Inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) messenger RNA (mRNA) expression in HL-60 leukemia cells by pentoxifylline and dexamethasone: dissociation of acivicin-induced TNF-alpha and IL-1 beta mRNA expression from acivicin-induced monocytoid differentiation. Weinberg, J.B., Mason, S.N., Wortham, T.S. Blood (1992) [Pubmed]
  29. Bile acids with differing hydrophilic-hydrophobic properties do not influence cytokine production by human monocytes and murine Kupffer cells. Bergamini, A., Dini, L., Baiocchi, L., Cappannoli, L., Falasca, L., Bolacchi, F., Capozzi, M., Faggioli, E., Nistri, A., Salanitro, A., Ventura, L., Rocchi, G., Angelico, M. Hepatology (1997) [Pubmed]
  30. The differential impact of disulfide bonds and N-linked glycosylation on the stability and function of CD14. Meng, J., Parroche, P., Golenbock, D.T., McKnight, C.J. J. Biol. Chem. (2008) [Pubmed]
  31. The CD14 region spanning amino acids 57-64 is critical for interaction with the extracellular Toll-like receptor 2 domain. Iwaki, D., Nishitani, C., Mitsuzawa, H., Hyakushima, N., Sano, H., Kuroki, Y. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  32. Cell distributions and functions of Toll-like receptor 4 studied by fluorescent gene constructs. Espevik, T., Latz, E., Lien, E., Monks, B., Golenbock, D.T. Scand. J. Infect. Dis. (2003) [Pubmed]
  33. Relative concentrations of endotoxin-binding proteins in body fluids during infection. Opal, S.M., Palardy, J.E., Marra, M.N., Fisher, C.J., McKelligon, B.M., Scott, R.W. Lancet (1994) [Pubmed]
  34. Lipopolysaccharide-coated erythrocytes activate human neutrophils via CD14 while subsequent binding is through CD11b/CD18. Troelstra, A., de Graaf-Miltenburg, L.A., van Bommel, T., Verhoef, J., Van Kessel, K.P., Van Strijp, J.A. J. Immunol. (1999) [Pubmed]
  35. Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. Kirschning, C.J., Wesche, H., Merrill Ayres, T., Rothe, M. J. Exp. Med. (1998) [Pubmed]
  36. Biochemical and functional characterization of membrane blebs purified from Neisseria meningitidis serogroup B. Post, D.M., Zhang, D., Eastvold, J.S., Teghanemt, A., Gibson, B.W., Weiss, J.P. J. Biol. Chem. (2005) [Pubmed]
  37. Interleukin 4 down-regulates the expression of CD14 in normal human monocytes. Lauener, R.P., Goyert, S.M., Geha, R.S., Vercelli, D. Eur. J. Immunol. (1990) [Pubmed]
  38. Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte/macrophage-colony-stimulating factor. Buelens, C., Verhasselt, V., De Groote, D., Thielemans, K., Goldman, M., Willems, F. Eur. J. Immunol. (1997) [Pubmed]
  39. Membrane-anchored CD14 is important for induction of interleukin-8 by lipopolysaccharide and peptidoglycan in uroepithelial cells. Shimizu, T., Yokota, S., Takahashi, S., Kunishima, Y., Takeyama, K., Masumori, N., Takahashi, A., Matsukawa, M., Itoh, N., Tsukamoto, T., Fujii, N. Clin. Diagn. Lab. Immunol. (2004) [Pubmed]
  40. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Bauer, S., Kirschning, C.J., Häcker, H., Redecke, V., Hausmann, S., Akira, S., Wagner, H., Lipford, G.B. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  41. Soluble MD-2 activity in plasma from patients with severe sepsis and septic shock. Pugin, J., Stern-Voeffray, S., Daubeuf, B., Matthay, M.A., Elson, G., Dunn-Siegrist, I. Blood (2004) [Pubmed]
  42. Granulomonocyte-associated lysosomal protein expression during in vitro expansion and differentiation of CD34+ hematopoietic progenitor cells. Scheinecker, C., Strobl, H., Fritsch, G., Csmarits, B., Krieger, O., Majdic, O., Knapp, W. Blood (1995) [Pubmed]
  43. Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi's sarcoma herpesvirus gene sequences. Raje, N., Gong, J., Chauhan, D., Teoh, G., Avigan, D., Wu, Z., Chen, D., Treon, S.P., Webb, I.J., Kufe, D.W., Anderson, K.C. Blood (1999) [Pubmed]
  44. 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. Schröder, N.W., Morath, S., Alexander, C., Hamann, L., Hartung, T., Zähringer, U., Göbel, U.B., Weber, J.R., Schumann, R.R. J. Biol. Chem. (2003) [Pubmed]
  45. The interaction of human peripheral blood eosinophils with bacterial lipopolysaccharide is CD14 dependent. Plötz, S.G., Lentschat, A., Behrendt, H., Plötz, W., Hamann, L., Ring, J., Rietschel, E.T., Flad, H.D., Ulmer, A.J. Blood (2001) [Pubmed]
  46. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. Cario, E., Rosenberg, I.M., Brandwein, S.L., Beck, P.L., Reinecker, H.C., Podolsky, D.K. J. Immunol. (2000) [Pubmed]
  47. Lipopolysaccharide binding protein expression in primary human hepatocytes and HepG2 hepatoma cells. Grube, B.J., Cochane, C.G., Ye, R.D., Green, C.E., McPhail, M.E., Ulevitch, R.J., Tobias, P.S. J. Biol. Chem. (1994) [Pubmed]
  48. Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. Stoffels, K., Overbergh, L., Giulietti, A., Verlinden, L., Bouillon, R., Mathieu, C. J. Bone Miner. Res. (2006) [Pubmed]
  49. Bactericidal/permeability-increasing protein preserves leukocyte functions after major liver resection. Wiezer, M.J., Meijer, C., Sietses, C., Prins, H.A., Cuesta, M.A., Beelen, R.H., Meijer, S., van Leeuwen, P.A. Ann. Surg. (2000) [Pubmed]
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