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CD14 molecule

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 3126

Nomenclature: CD14 molecule

Family: CD molecules

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 375 5q31.3 CD14 CD14 molecule
Previous and Unofficial Names Click here for help
myeloid cell-specific leucine-rich glycoprotein
Database Links Click here for help
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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Antibodies
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Antibody Sp. Action Value Parameter Reference
atibuclimab Peptide Immunopharmacology Ligand Hs Binding - - 1,4
[1,4]
Antibody Comments
The use of anti-CD14 monoclonal antibodies to treat viral infection is claimed in Implicit Bioscience's patent WO2018165720A1. Their clinical candidate IC14 which was derived from murine clone 28C5, is claimed in this patent.
Immunopharmacology Comments
Because of its key role in amplifying the immune response, CD14 is being targeted for pharmacological modulation. Implicit Bioscience have a first-in-class anti-CD14 monoclonal antbody clinical lead, IC14 [6-7], that is being evaluated for imunomodulatory potential in ALS/MND. IC14 has also been tested for acute respiratory distress syndrome (ARDS) and sepsis [1,4,7].

In April 2020, in response to the COVID-19 pandemic, Implicit initiated a clinical trial (NCT04346277) to investigate the potential of CD14 modulation as a mechanism to mitigate against cytokine storm and ARDS in patients with this potentially deadly disease. IC14 is predicted to prevent CD14 from participating in the recognition of PAMPs and DAMPs that are generated during SARS-CoV-2 infection.
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   monocyte (CL:0000576)
References:  5
Tissue Distribution Click here for help
CD14 is present on immune cells (macrophages, monocytes, Kupffer cells, neutrophils and B cells), endothelial cells and epithelial cells.
Species:  Human
Technique: 
References:  3
Physiological Consequences of Altering Gene Expression Click here for help
Cd14 knockout is not lethal. Cd14–/– mice infected with Gram‐negative bacteria appear less clinically ill than wild‐type controls, and have smaller bacterial burdens in organs (bone marrow, lungs and spleen). Cd14 deficiency confers resistance to endotoxin shock.
Species:  Mouse
Tissue: 
Technique: 
References:  2
General Comments
CD14 acts as a scavenger receptor for bacterial lipopolysaccharide. It is present as a phosphatidylinositol phospholipid anchored membrane protein and in circulating soluble form [5]. CD14 recognises LPS bound to lipopolysaccharide-binding protein (LBP; HGNC 6517) and delivers it to the LY96/TLR4 complex, to amplify the inflammatory response to pathogens and to DAMPS. Engagement of the TLR pathway results in signals that prompt leukocyte recruitment, NF-κB activation and cytokine secretion.

References

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1. Axtelle T, Pribble J. (2001) IC14, a CD14 specific monoclonal antibody, is a potential treatment for patients with severe sepsis. J Endotoxin Res, 7 (4): 310-4. [PMID:11717588]

2. Haziot A, Ferrero E, Köntgen F, Hijiya N, Yamamoto S, Silver J, Stewart CL, Goyert SM. (1996) Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. Immunity, 4 (4): 407-14. [PMID:8612135]

3. Jersmann HP. (2005) Time to abandon dogma: CD14 is expressed by non-myeloid lineage cells. Immunol Cell Biol, 83 (5): 462-7. [PMID:16174094]

4. Reinhart K, Glück T, Ligtenberg J, Tschaikowsky K, Bruining A, Bakker J, Opal S, Moldawer LL, Axtelle T, Turner T et al.. (2004) CD14 receptor occupancy in severe sepsis: results of a phase I clinical trial with a recombinant chimeric CD14 monoclonal antibody (IC14). Crit Care Med, 32 (5): 1100-8. [PMID:15190957]

5. Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B. (1989) Monocyte antigen CD14 is a phospholipid anchored membrane protein. Blood, 73 (1): 284-9. [PMID:2462937]

6. Spek CA, Verbon A, Aberson H, Pribble JP, McElgunn CJ, Turner T, Axtelle T, Schouten J, Van Der Poll T, Reitsma PH. (2003) Treatment with an anti-CD14 monoclonal antibody delays and inhibits lipopolysaccharide-induced gene expression in humans in vivo. J Clin Immunol, 23 (2): 132-40. [PMID:12757265]

7. Verbon A, Dekkers PE, ten Hove T, Hack CE, Pribble JP, Turner T, Souza S, Axtelle T, Hoek FJ, van Deventer SJ et al.. (2001) IC14, an anti-CD14 antibody, inhibits endotoxin-mediated symptoms and inflammatory responses in humans. J Immunol, 166 (5): 3599-605. [PMID:11207321]

How to cite this page

CD molecules: CD14 molecule. Last modified on 11/11/2020. Accessed on 28/10/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3126.