C-C motif chemokine 11 also known as eosinophil chemotactic protein and eotaxin-1 is a protein that in humans is encoded by the CCL11gene. This gene is encoded on three exons and is located on chromosome 17.[1][2]
CCL11 is a small cytokine belonging to the CC chemokine family. CCL11 selectively recruits eosinophils by inducing their chemotaxis, and therefore, is implicated in allergic responses.[3][4][5] The effects of CCL11 are mediated by its binding to a G-protein-linked receptor known as a chemokine receptor. Chemokine receptors for which CCL11 is a ligand include CCR2,[6]CCR3[1] and CCR5.[6] However, it has been found that eotaxin-1 (CCL11) has high degree selectivity for its receptor, such that they are inactive on neutrophils and monocytes, which do not express CCR3.[7]
Increased CCL11 levels in blood plasma are associated with aging in mice and humans.[8] Additionally, it has been demonstrated that exposing young mice to CCL11 or the blood plasma of older mice decreases their neurogenesis and cognitive performance on behavioural tasks thought to be dependent on neurogenesis in the hippocampus.[8]
Higher plasma concentrations of CCL11 have been found in current cannabis users compared to past users and those who had never used. CCL11 has also been found in higher concentrations in people suffering from schizophrenia; cannabis is a known trigger of schizophrenia.[9]
During periods of bone inflammation, CCL11 and CCR3 are upregulated. This is associated with an increase in osteoclast activity.[11]
References
↑ 1.01.1Kitaura M, Nakajima T, Imai T, Harada S, Combadiere C, Tiffany HL, Murphy PM, Yoshie O (Mar 1996). "Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3". The Journal of Biological Chemistry. 271 (13): 7725–30. doi:10.1074/jbc.271.13.7725. PMID8631813.
↑Hein H, Schlüter C, Kulke R, Christophers E, Schröder JM, Bartels J (Aug 1997). "Genomic organization, sequence, and transcriptional regulation of the human eotaxin gene". Biochemical and Biophysical Research Communications. 237 (3): 537–42. doi:10.1006/bbrc.1997.7169. PMID9299399.
↑Garcia-Zepeda EA, Rothenberg ME, Ownbey RT, Celestin J, Leder P, Luster AD (Apr 1996). "Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia". Nature Medicine. 2 (4): 449–56. doi:10.1038/nm0496-449. PMID8597956.
↑ 6.06.1Ogilvie P, Bardi G, Clark-Lewis I, Baggiolini M, Uguccioni M (Apr 2001). "Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5". Blood. 97 (7): 1920–4. doi:10.1182/blood.V97.7.1920. PMID11264152.
↑Fernandez-Egea E, Scoriels L, Theegala S, Giro M, Ozanne SE, Burling K, Jones PB (Oct 2013). "Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 46: 25–8. doi:10.1016/j.pnpbp.2013.06.011. PMID23820464.
Garcia-Zepeda EA, Rothenberg ME, Ownbey RT, Celestin J, Leder P, Luster AD (Apr 1996). "Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia". Nature Medicine. 2 (4): 449–56. doi:10.1038/nm0496-449. PMID8597956.
Kitaura M, Nakajima T, Imai T, Harada S, Combadiere C, Tiffany HL, Murphy PM, Yoshie O (Mar 1996). "Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3". The Journal of Biological Chemistry. 271 (13): 7725–30. doi:10.1074/jbc.271.13.7725. PMID8631813.
Bartels J, Schlüter C, Richter E, Noso N, Kulke R, Christophers E, Schröder JM (Aug 1996). "Human dermal fibroblasts express eotaxin: molecular cloning, mRNA expression, and identification of eotaxin sequence variants". Biochemical and Biophysical Research Communications. 225 (3): 1045–51. doi:10.1006/bbrc.1996.1292. PMID8780731.
Garcia-Zepeda EA, Rothenberg ME, Weremowicz S, Sarafi MN, Morton CC, Luster AD (May 1997). "Genomic organization, complete sequence, and chromosomal location of the gene for human eotaxin (SCYA11), an eosinophil-specific CC chemokine". Genomics. 41 (3): 471–6. doi:10.1006/geno.1997.4656. PMID9169149.
Hein H, Schlüter C, Kulke R, Christophers E, Schröder JM, Bartels J (Aug 1997). "Genomic organization, sequence, and transcriptional regulation of the human eotaxin gene". Biochemical and Biophysical Research Communications. 237 (3): 537–42. doi:10.1006/bbrc.1997.7169. PMID9299399.
Nibbs RJ, Wylie SM, Yang J, Landau NR, Graham GJ (Dec 1997). "Cloning and characterization of a novel promiscuous human beta-chemokine receptor D6". The Journal of Biological Chemistry. 272 (51): 32078–83. doi:10.1074/jbc.272.51.32078. PMID9405404.
Rubbert A, Combadiere C, Ostrowski M, Arthos J, Dybul M, Machado E, Cohn MA, Hoxie JA, Murphy PM, Fauci AS, Weissman D (Apr 1998). "Dendritic cells express multiple chemokine receptors used as coreceptors for HIV entry". Journal of Immunology. 160 (8): 3933–41. PMID9558100.
Noso N, Bartels J, Mallet AI, Mochizuki M, Christophers E, Schröder JM (Apr 1998). "Delayed production of biologically active O-glycosylated forms of human eotaxin by tumor-necrosis-factor-alpha-stimulated dermal fibroblasts". European Journal of Biochemistry / FEBS. 253 (1): 114–22. doi:10.1046/j.1432-1327.1998.2530114.x. PMID9578468.
Crump MP, Rajarathnam K, Kim KS, Clark-Lewis I, Sykes BD (Aug 1998). "Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation". The Journal of Biological Chemistry. 273 (35): 22471–9. doi:10.1074/jbc.273.35.22471. PMID9712872.
Sabroe I, Hartnell A, Jopling LA, Bel S, Ponath PD, Pease JE, Collins PD, Williams TJ (Mar 1999). "Differential regulation of eosinophil chemokine signaling via CCR3 and non-CCR3 pathways". Journal of Immunology. 162 (5): 2946–55. PMID10072545.
Jinquan T, Quan S, Feili G, Larsen CG, Thestrup-Pedersen K (Apr 1999). "Eotaxin activates T cells to chemotaxis and adhesion only if induced to express CCR3 by IL-2 together with IL-4". Journal of Immunology. 162 (7): 4285–92. PMID10201960.
Klein RS, Williams KC, Alvarez-Hernandez X, Westmoreland S, Force T, Lackner AA, Luster AD (Aug 1999). "Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS". Journal of Immunology. 163 (3): 1636–46. PMID10415069.
Blanpain C, Migeotte I, Lee B, Vakili J, Doranz BJ, Govaerts C, Vassart G, Doms RW, Parmentier M (Sep 1999). "CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist". Blood. 94 (6): 1899–905. PMID10477718.
Zhang J, Lathbury LJ, Salamonsen LA (Feb 2000). "Expression of the chemokine eotaxin and its receptor, CCR3, in human endometrium". Biology of Reproduction. 62 (2): 404–11. doi:10.1095/biolreprod62.2.404. PMID10642580.
Kampen GT, Stafford S, Adachi T, Jinquan T, Quan S, Grant JA, Skov PS, Poulsen LK, Alam R (Mar 2000). "Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases". Blood. 95 (6): 1911–7. PMID10706854.
Huber MA, Kraut N, Addicks T, Peter RU (Mar 2000). "Cell-type-dependent induction of eotaxin and CCR3 by ionizing radiation". Biochemical and Biophysical Research Communications. 269 (2): 546–52. doi:10.1006/bbrc.2000.2287. PMID10708591.