CD14

What is CD14?

CD14 (cluster of differentiation 14), formerly known as MY23 antigen, is a surface antigen and a member of the cell surface glycoprotein family. It is a ubiquitous pattern recognition receptor. CD14 is the cell membrane receptor of bacterial lipopolysaccharide (LPS). It recognizes and binds LPS, to induce cellular tyrosine phosphorylation, nuclear factor NF-κB translocation, cytokine release and production of oxygen free radicals. It plays an important role in a series of reactions caused by immune and defense systems.

CD14 exists in two forms, one is the cell membrane CD14, is immobilized on the membrane through the glycosylphosphatidylinositol tail (mCD14), and the other is the soluble form (sCD14).

The Structure of CD14

The CD14 gene is located in the 5q23-31 region of the long arm of human chromosome 5, about 3900 bp.

The precursor protein encoded by the gene is a polypeptide chain consisting of 375 amino acids, which removes the first 19 signal peptides of the precursor peptide to form a mature membrane-type CD14.

The 39-44 residue at the N-terminal is the most basic part of the human CD14-LPS binding site.

The residues 86-329 contain 10 repetitive characteristic sequences rich in leucine, which can interact with lipids to form a hydrophilic β-sheet, which may play an important role in protein-protein recognition.

The carboxyl terminal of CD14 amino acid sequence contains 17 hydrophobic neutral amino acids and 5 N-glycosyl binding sites.

mCD14 is a 55 kDa glycoprotein without transmembrane domain.

The molecular weight of sCD14 is smaller than that of mCD14. There are two kinds of soluble CD14: sCD14a and sCD14 β, their molecular weights are 49 kDa and 55 kDa respectively.

The Expression of CD14

The expression of CD14 in human and mouse is tissue-specific and cell-specific.

mCD14 protein is preferentially expressed on the surface of monocytes, macrophages and dendritic cells. In addition, mCD14 was also found in neutrophils' endoplasmic secretory bodies and aniline granules.

sCD14 exists in the plasma (serum) of normal people and animals. The normal concentration of sCD14 in human serum is 2-5 mg/mL, accounting for 99% of the total CD14 content in blood. sCD14 is also found in trace amounts in urine.

The Ligands of CD14

The ligands of mCD14 include lipopolysaccharide (LPS), peptide polysaccharides, teichoic acid, lipopeptides and many other microbial signals. In addition, endogenous ligands such as heat shock protein 60, ceramide, phospholipids and lipoproteins can also be recognized by mCD14. The ligands of CD14 also include peptidoglycan (PGN) from the cell wall of Gram-positive bacteria, lipoarabinomannan from Mycobacterium and various pathogens.

The Function of CD14

CD14 is a ubiquitous pattern recognition receptor. As the cell membrane receptor of bacterial lipopolysaccharide, it cooperates with other proteins and plays a key role in a series of pathological reactions caused by immune and defense system.

The interaction between mCD14 and its ligand LPS/LBP can make the target cells produce cytokines, which can induce immune response and pathological injury.

CD14 not only participates in cell activation as a LPS receptor, but also has other functions. CD14 is one of the receptors that recognize and phagocytize apoptotic cells in macrophages.

CD14 is associated with many diseases and plays a dual role in host anti-infection. It can be beneficial to the host by inducing sufficient inflammatory and immune responses to eliminate invasive microorganisms. It can also adversely affect the host due to excessive inflammation.

The diseases related to CD14 mainly include sepsis, immune system disease, cardiovascular system disease and chronic kidney disease and so on.

Applications of CD14 in Treatment

At present, there are relatively few researches on CD14. IC-14, a CD14-related drug, is still in clinical research for acute lung injury, septic shock, and adult respiratory distress syndrome.

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