CD14 LPS receptor (LPS-R)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
GPI anchor
Monocyte
Macrophage
Langerhans Cell
Cytokine
Granulocyte
Plasma
Osteoclast
Hepatocyte
Epithelial Cell
Microglia
53 / 53
55 / 55

Expression
CD14 is expressed strongly on the surface of monocytes, osteoclast progenitors and macrophages and weaker on the surface of granulocytes, on tissue macrophages, Langerhans cells and microglia but not expressed by myeloid progenitors.  It can be induce Rd with certain cytokines or fMLP. IFN-g or IL-13 treatment decreases expression on monocytes.  In mice stimulated with lipopolysaccharide (LPS), CD14 expression is detected in non-myeloid cell types like hepatocytes and several epithelial cell types.  Soluble forms can be detected in plasma serum and tissue culture supernatants of cells transfected with CD14.  The antigen has also been detected, at low levels, on human B cells.  The level of expression on granulocytes is higher in rabbits and goats than in other species that have been examined.


Structure
MOLECULAR FAMILY NAME:  Belongs to the lipopolysaccharide receptor family.

CD14 is a GPI-anchored 356 aa glycoprotein.  It contains a 19aa signal peptide, an extracellular domain which contain 11 leucine-rich repeat (LRR) domains, 4 N-glycosylation sites and an unknown number of O-glycosylation sites.  These LRR domains, however do not show the regular size or enough of the sequence patterns characteristic of LRR repeats to be included in this family.  At least 2 soluble forms of CD14 have been described, one retains GPI and is released from the cell surface which results in an approximately 48 kDa molecule and the other i s released prior to the addition of the GPI anchor resulting in a higher molecular weight (>48 kDa).  The CD14 gene contains a single 88 base pair intron immediately following the initiation condon and maps to a chromosome region with other genes encoding growth factors and receptor.  In humans, this chromosomal region containing other genes encodes growth factors such as IL-3, IL-4, IL-5, IL-9, GM-CSF and receptors such as M-CSFR, PDGFR, a1 - and b2-adrenergic receptors.  Soluble forms of CD14 are present in normal serum and urine of nephrotic patients and the culture media of cells expressing CD14.   

MOLECULAR MASS
Cell Type Unreduced Reduced
Monocytes 53 kDa 55 kDa post

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD14 is N-linked glycosylation and the GPI-anchor is at the C-terminus.

Ligands
CD14 is a receptor for the complex of LPS and the LPS-binding protein (LBP).  The complex may be associated with the Toll-like receptor 2, depending on species.

LIGANDS AND MOLECULES ASSOCIATED WITH CD14
Molecule Comment
Endotoxin (lipopolysaccharide) Direct binding data indicate that each CD14 molecule binds 1-2 molecules of LPS. The binding of LPS to CD14 is accelerated in the presence of LBP.
Lipoteichoic acid In vitro binding studies show that lipoteichoic acid and phosphatidylinositol bind to sCD14. The physiological relevance of this binding has not yet been demonstrated.
Phosphatidylinositol In vitro binding studies show that lipoteichoic acid and phosphatidylinositol bind to sCD14. The physiological relevance to this binding has not yet been demonstrated.

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 suggest that a non-covalently linked hydrophobic contaminant of the peptidoglycan is the substance that binds CD14.



Function
CD14 functions as a receptor for endotoxin LPS and have been shown to bind apoptotic cells.  LPS binds to a serum protein, LBP which facilitates the binding of LPS to CD14.  When LPS binds to CD14 expressed on monocytes or neutrophils, the cells become activated and release cytokines such as TNF and upregulate cell suface 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 CD15 like endothelial cells and some epithelial cells.  This stimulation occurs through an unidentified receptor to secrete cytokines and upregulate adhesion molecules.  TNFa synthesis induced by LPS in monocytes and macrophages can be blocked by anti-CD14 mAbs. The interaction of CD14 with the LPS-LBP complex causes an increase in the adhesive activity of  CD11b/CD18 CR3 on neutrophils. Transgenic mice overexpressing human CD14 show increased susceptibility to endotoxin shock, whereas CD14-deficient mice are highly resistant to either live gram-negative bacteria or LPS.  CD14-deficient mice also show dramatically reduced levels of bacteremia following in vivo challenge with E. coli, suggesting a role for CD14 in dissemination of gram-negative bacteria.

BIOCHEMICAL ACTIVITY

CD14 is a receptor for endotoxin LPS.  Some studies suggest that sCD14 may act, in concert with LBP, as a lipid transfer molecule.

DISEASE RELEVANCE AND FUNCTION OF CD14 IN INTACT ANIMAL

CD14 is required for induction of cytokines and/or lethality in murine model of shock induced endotoxin or live E. coli 0111.  Soluble forms of CD14 are found in plasma at a concentration of about 3 mg/ml.  In whole blood, the amount of soluble CD14 exceeds the amount of membrane-bound CD14 by 2-3 logs.  Deletions in the chromosomal region of CD14 are frequently found in myeloid leukemias

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD14: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD14
Molecule Comment
LBP (Lipopolysaccharide binding protein) LBP is a lipid protein that moves monomers of LPS, phosphatidylinositol, and other phoisholipids to a binding site on CD14.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrexgene 929P08571
MouseS03605P10810M34510
Antibodies
CAM36A   View Reactivity
CAM66A   View Reactivity
M5E2   View Reactivity
MIL2   View Reactivity
MM61A   View Reactivity
MOP9   View Reactivity
TUK4   View Reactivity
UCHM1   View Reactivity
VPM65   View Reactivity

Revised June 25, 2008


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