CCL2
For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.
| edit |
Chemokine (C-C motif) ligand 2 (CCL2) is a small cytokine belonging to the CC chemokine family that is also known as monocyte chemotactic protein-1 (MCP-1) and small inducible cytokine A2. CCL2 recruits monocytes, memory T cells, and dendritic cells to sites of tissue injury and infection.[1][2]
Contents |
[edit] Genomics
As with many other CC chemokines, CCL2 is located on chromosome 17 (17q11.2-q21.1) in humans.[3]The gene spans 1,927 bases and lies on the Watson (plus) strand. The gene has three exons and two introns. It is produced as a protein precursor containing signal peptide of 23 amino acids and a mature peptide of 76 amino acids.[4][5] The predicted weight is 11.025 kiloDaltons (kDa).
In the mouse the homolog is Sig-je.
[edit] Population genetics
The levels of this protein vary considerably between normal people. Multivariable-adjusted heritability of MCP-1 concentrations in whites of European descent has been reported to be 0.37 in plasma and 0.44 in serum[6][7]
[edit] Molecular biology
It is a monomeric polypeptide, with a molecular weight of approximately 13kDa. It is tethered on endothelial cells by glycosaminoglycan side chains of proteoglycans. It is primarily secreted by monocytes, macrophages and dendritic cells. It is a platelet derived growth factor inducible gene. It is cleaved by the metalloproteinase MMP-12.
The cell surface receptors that bind CCL2 are CCR2 and CCR4.[8]
This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. Deletion of the N-terminal residue converts it from an activator of basophils to an eosinophil chemoattractant. CCL2 causes the degranulation of basophils and mast cells, an effect potentiated by pre-treatment with IL-3 and other cytokines.[9][10] It augments monocyte anti-tumor activity and is essential for granuloma formation
It is found at the site of tooth eruption and bone degradation. In the bone, CCL2 is expressed by mature osteoclasts and osteoblasts and is under the control of nuclear factor κB (NFκB). In human osteoclasts, it has been shown that CCL2 and RANTES (regulated on activation normal T cell expressed and secreted) are unregulated by RANKL (receptor activator of NFκB ligand).[[[Category:All articles with unsourced statements]][citation needed]] Both MCP-1 and RANTES were also shown to induce the formation of TRAP-positive, multinuclear cells from M-CSF-treated monocytes in the absence of RANKL, but produced osteoclasts that lacked cathepsin K expression and resorptive capacity. It is proposed that CCL2 and RANTES act as autocrine loop in human osteoclast differentiation.[11]
The CCL2 chemokine is also expressed by neurons, astrocytes and microglia in nervous tissue. Neuronal expression of CCL2 is mainly found in the cerebral cortex, globus pallidus, hippocampus, paraventricular and supraoptic hypothalamic nuclei, lateral hypothalamus, substantia nigra, facial nuclei, motor and spinal trigeminal nuclei, gigantocellular reticular nucleus and in Purkinje cells in the cerebellum. [12]
[edit] Clinical importance
CCL2 has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. [13]
Recent data indicates an important role for CCL2 in the neuroinflammatory processes that takes place in various central nervous system (CNS) diseases characterized by neuronal degeneration.[14] Its expression by glial cells is increased in epilepsy[15][16], brain ischemia[11], Alzheimer’s disease[17], experimental autoimmune encephalomyelitis (EAE)[18], and traumatic brain injury.[19]
[edit] References
- ^ Carr MW, Roth SJ, Luther E, Rose SS, Springer TA (April 1994). "Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant". Proc. Natl. Acad. Sci. U.S.A. 91 (9): 3652–6. doi:10.1073/pnas.91.9.3652. PMID 8170963.
- ^ Xu LL, Warren MK, Rose WL, Gong W, Wang JM (1 September 1996). "Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro". J. Leukoc. Biol. 60 (3): 365–71. PMID 8830793. http://www.jleukbio.org/cgi/pmidlookup?view=long&pmid=8830793.
- ^ Mehrabian M, Sparkes RS, Mohandas T, Fogelman AM, Lusis AJ (January 1991). "Localization of monocyte chemotactic protein-1 gene (SCYA2) to human chromosome 17q11.2-q21.1". Genomics 9 (1): 200–3. doi:10.1016/0888-7543(91)90239-B. PMID 2004761.
- ^ Yoshimura T, Yuhki N, Moore SK, Appella E, Lerman MI, Leonard EJ (February 1989). "Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE". FEBS Lett. 244 (2): 487–93. doi:10.1016/0014-5793(89)80590-3. PMID 2465924.
- ^ Furutani Y, Nomura H, Notake M, Oyamada Y, Fukui T, Yamada M, Larsen CG, Oppenheim JJ, Matsushima K (February 1989). "Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF)". Biochem. Biophys. Res. Commun. 159 (1): 249–55. doi:10.1016/0006-291X(89)92430-3. PMID 2923622.
- ^ McDermott DH, Yang Q, Kathiresan S et al. (2005) CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study. Circulation 112(8):1113–1120
- ^ Bielinski SJ, Pankow JS, Miller MB, et al (2007)Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI family heart study follow-up examination. Genes Immun. 8(8):684–690
- ^ Craig MJ, Loberg RD (December 2006). "CCL2 (Monocyte Chemoattractant Protein-1) in cancer bone metastases". Cancer Metastasis Rev. 25 (4): 611–9. doi:10.1007/s10555-006-9027-x. PMID 17160712.
- ^ Conti P, Boucher W, Letourneau R, Feliciani C, Reale M, Barbacane RC, Vlagopoulos P, Bruneau G, Thibault J, Theoharides TC (November 1995). "Monocyte chemotactic protein-1 provokes mast cell aggregation and [3H5HT release"]. Immunology 86 (3): 434–40. PMID 8550082.
- ^ Bischoff SC, Krieger M, Brunner T, Dahinden CA (May 1992). "Monocyte chemotactic protein 1 is a potent activator of human basophils". J. Exp. Med. 175 (5): 1271–5. doi:10.1084/jem.175.5.1271. PMID 1569397.
- ^ a b Kim MS, Day CJ, Morrison NA (2005). "MCP-1 is induced by receptor activator of nuclear factor-{kappa}B ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation". J Biol Chem 280 (16): 16163-9. doi:10.1074/jbc.M412713200. PMID 15722361. http://www.jbc.org/content/280/16/16163?cited-by=yes&legid=jbc;280/16/16163.
- ^ Banisadr G, Gosselin RD, Mechighel P, Kitabgi P, Rostène W, Parsadaniantz SM (2005). "Highly regionalized neuronal expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) in rat brain: evidence for its colocalization with neurotransmitters and neuropeptides.". J Comp Neurol 489 (3): 275-92. doi:10.1002/cne.20598. PMID 16025454.
- ^ Xia M, Sui Z. (2009). "Recent developments in CCR2 antagonists.". Expert Opin Ther Pat 19 (3): 295-303. doi:10.1517/13543770902755129. PMID 19441905. http://informahealthcare.com/doi/abs/10.1517/13543770902755129.
- ^ Gerard C, Rollins BJ. (2001). "Chemokines and disease.". Nat Immunol. 2: 108-115. doi:10.1038/84209. PMID 11175802. http://www.nature.com/ni/journal/v2/n2/full/ni0201_108.html.
- ^ Foresti ML, Arisi GM, Katki K, Montañez A, Sanchez RM, Shapiro LA. (2009). "Chemokine CCL2 and its receptor CCR2 are increased in the hippocampus following pilocarpine-induced status epilepticus.". J Neuroinflammation 6: 40-51. doi:10.1186/1742-2094-6-40. PMID 20034406. http://www.jneuroinflammation.com/content/6/1/40.
- ^ Fabene PF, Bramanti P, Constantin G. (2010). "The emerging role for chemokines in epilepsy.". J Neuroimmunol 224: 22-27. doi:10.1016/j.jneuroim.2010.05.016. PMID 20542576. http://www.jni-journal.com/article/S0165-5728%2810%2900200-6/abstract.
- ^ Hickman SE, El Khoury J. (2010). "Mechanisms of mononuclear phagocyte recruitment in Alzheimer's disease.". CNS Neurol Disord Drug Targets. 9 (2): 168-173. PMID 20205643. http://www.benthamdirect.org/pages/b_viewarticle.php?3158683.
- ^ Ransohoff RM, Hamilton TA, Tani M, Stoler MH, Shick HE, Major JA, Estes ML, Thomas DM, Tuohy VK. (1993). "Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis.". FASEB J. 7: 592-600. PMID 8472896. http://www.fasebj.org/cgi/reprint/7/6/592.
- ^ Semple BD, Bye N, Rancan M, Ziebell JM, Morganti-Kossmann MC. (2010). "Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2-/- mice.". J Cereb Blood Flow Metab. 30 (4): 769-782. doi:10.1038/jcbfm.2009.262. PMID 20029451. http://www.nature.com/jcbfm/journal/v30/n4/full/jcbfm2009262a.html.
[edit] Further reading
- Yoshimura T, Leonard EJ (1992). "Human monocyte chemoattractant protein-1 (MCP-1).". Adv. Exp. Med. Biol. 305: 47–56. PMID 1661560.
- Wahl SM, Greenwell-Wild T, Hale-Donze H, et al. (2000). "Permissive factors for HIV-1 infection of macrophages.". J. Leukoc. Biol. 68 (3): 303–10. PMID 10985244.
- Sell H, Eckel J (2007). "Monocyte chemotactic protein-1 and its role in insulin resistance.". Curr. Opin. Lipidol. 18 (3): 258–62. doi:10.1097/MOL.0b013e3281338546. PMID 17495598.
|
|
 |
This article on a gene on chromosome 17 is a stub. You can help Wikipedia by expanding it. |
