• LPS receptor, LPS-R

MAJOR LINKS FOR CD14  

• NCBI LocusLink Record: 929
• Mendelian Inheritance in Man (OMIM): 158120
• SwissProt annotated protein record: P08571

• Receptor for endotoxin. (Wright et al. 1990)
• Some studies suggest that sCD14 may act, in concert with LBP, as a lipid transfer molecule (Hailman et al. 1994, Yu et al. 1997)

CELLULAR FUNCTION OF CD14  

• CD14 functions as a receptor for endotoxin (lipopolysaccharide [LPS]). (Wright et al. 1990)*
• LPS binds to a serum protein, LBP (LPS-binding protein) which facilitates the binding of LPS to CD14 (Hailman et al. 1994)*
• When LPS binds to CD14 expressed by monocytes or neutrophils, the cells become activated and release cytokines such as tumor necrosis factor (TNF) and up-regulate cell surface molecules, including adhesion molecules
• In vitro studies show that sCD14 can bind to LPS. The sCD14/LPS complex can then stimulate cells, which do not express membrane CD14 (eg. endothelial cells and some epithelial cells); this stimulation occurs through an unidentified receptor to secrete cytokines and upregulate adhesion molecules (Haziot et al. 1993, Pugin et al. 1994)

DISEASE RELEVANCE OF CD14 AND FUNCTION OF CD14 IN INTACT ANIMAL  

• Required for induction of cytokines and/or lethality in murine model of shock induced endotoxin or live E. Coli 0111. (Haziot et al. 1996)
• Soluble forms of CD14 are found in plasma at a concentration of about 3 ug/ml**
• In whole blood, the amount of soluble CD14 exceeds the amount of membrane-bound CD14 by 2-3 logs**

MOLECULAR STRUCTURE OF CD14  

• The mature CD14 membrane protein is composed of 356 amino acids with 4 sites for N-linked glycosylation. An additional 19 amino acid signal sequence is removed during processing
• CD14 is anchored to the cell surface by linkage to glycosylphosphatidylinositol
• At least two soluble forms of CD14 (sCD14) have been described
• One soluble form is produced by shedding the cell surface form, which results in an approximately 48 kDa molecule (Bazil et al. 1986, 1991; Haziot et al. 1988, 1993)
• A second soluble form is released from cells before addition of the GPI anchor, resulting in a higher molecular weight (LaBeta et al. 1993, Landmann et al. 1995, Bufler et al. 1995
• The CD14 gene contains a single, 88 base pair intron immediately following the initiation codon

MOLECULAR MASS OF CD14  

POST-TRANSCRIPTIONAL MODIFICATION OF CD14   - No information

POST-TRANSLATIONAL MODIFICATION OF CD14  

• N-linked glycosylation
• GPI anchor at C-terminus**

SUBSTRATES FOR CD14   - No information

ENZYMES WHICH MODIFY CD14  

LIGANDS FOR CD14 AND MOLECULES ASSOCIATED WITH CD14  

• Indirect studies suggest that CD14 may also bind lipoarabinomannan, peptidoglycan, and manuronic acids. While it is clear that peptidoglycan preparations stimulate cells in a CD14-dependent fashion, recent data suggests that a noncovalently linked hydrophobic contaminant of the peptidoglycan is the substance that binds CD14*

• Expressed strongly on the surface of monocytes and weakly on the surface of granulocytes; also expressed by most tissue macrophages
• Not expressed by myeloid progenitors
• In mice stimulated with lipopolysaccharide (LPS), CD14 expression is detected in non-myeloid cell types (eg. Hepatocytes and several epithelial cell types)(Fearns et al. 1995)
• Soluble forms of CD14 can be detected in serum and tissue culture supernatants of cells transfected with CD14

• The gene is located at 5q23-31

SELECTION OF OTHER CD14-SPECIFIC REFERENCE MAB  

REVIEWS

PRIMARY CITATIONS

1. Bazil V and Strominger JL. Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes. J. Immunol. 1991 147:1567 PubMed

2. Bazil V, Horejsi V, Baudys M, Kristofova H, Strominger JL, Kostka W and Hilgert I. Biochemical characterization of a soluble form of the 53-kDa monocyte surface antigen. Eur. J. Immunol. 1986 16:1583 PubMed

3. Bufler P, Stiegler G, Schuchmann M, Hess S, Kruger C, Stelter F, Eckerskorn C, Schutt C and Engelmann H. Soluble lipopolysaccharide receptor (CD14) is released via two different mechanisms from human monocytes and CD14 transfectants. Eur. J. Immunol. 1995 25:604 PubMed

4. Fearns C, Kravchenko VV, Ulevitch RJ and Loskutoff DJ. Murine CD14 gene expression in vivo: extramyeloid synthesis and regulation by lipopolysaccharide. J. Exp. Med. 1995 181:857 PubMed

5. Ferrero E and Goyert SM. Nucleotide sequence of the gene encoding the monocyte differentiation antigen, CD14. Nucleic Acids Res. 1988 16:4173 PubMed

6. Goyert SM, Ferrero E, Rettig WJ, Yenamandra AK, Obata F and Le Beau MM. The CD14 monocyte differentiation antigen maps to a region encoding growth factors and receptors. Science 1988 239:497 PubMed

7. Goyert SM, Ferrero EM, Seremetis SV, Winchester RJ, Silver J and Mattison AC. Biochemistry and expression of myelomonocytic antigens. J. Immunol. 1986 137:3909 PubMed

8. Hailman E, Lichenstein HS, Wurfel MM, Miller DS, Johnson DA, Kelley M, Busse LA, Zukowski MM and Wright SD. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J. Exp. Med. 1994 179:269 ** PubMed

9. Haziot A, Chen S, Ferrero E, Low MG, Silber R and Goyert SM. The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J. Immunol. 1988 141:547 PubMed

10. Haziot A, Ferrero E, Kontgen F, Hijiya N, Yamamoto S, Silver J, Stewart CL and Goyert SM. Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. Immunity 1996 4:407 PubMed

11. Haziot A, Tsuberi BZ and Goyert SM. Neutrophil CD14: biochemical properties and role in the secretion of tumor necrosis factor-alpha in response to lipopolysaccharide. J. Immunol. 1993 150:5556 PubMed

12. Haziot, A., Katz, I., Jiao, D., Rong, G,-W., and Goyert, S.M. Functional epitopes of CD14. In Leukocyte Typing V: White cell differentiation antigens. (Eds. S. Schlossman, et al.) Oxford University Press, pp. 782-784,(1995)

13. Labeta MO, Durieux JJ, Fernandez N, Herrmann R and Ferrara P. Release from a human monocyte-like cell line of two different soluble forms of the lipopolysaccharide receptor, CD14. Eur. J. Immunol. 1993 23:2144 PubMed

14. Landmann R, Zimmerli W, Sansano S, Link S, Hahn A, Glauser MP and Calandra T. Increased circulating soluble CD14 is associated with high mortality in gram-negative septic shock. J. Infect. Dis. 1995 171:639 PubMed

15. Pugin J, Ulevitch RJ and Tobias PS. Activation of endothelial cells by endotoxin: direct versus indirect pathways and the role of CD14. Prog. Clin. Biol. Res. 1994 392:369 PubMed

16. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ and Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 1990 249:1431 ** PubMed

17. Wurfel MM, Hailman E and Wright SD. Soluble CD14 acts as a shuttle in the neutralization of lipopolysaccharide (LPS) by LPS-binding protein and reconstituted high density lipoprotein. J. Exp. Med. 1995 181:1743 ** PubMed

18. Yu B, Hailman E and Wright SD. Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids. J. Clin. Invest. 1997 99:315 ** PubMed

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Modified 10/14/99   mpr@mail.nih.gov