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Chemokines, or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.
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Chemokine ligand 5 is a protein which in humans is encoded by the CCL5 gene. The gene has been discovered in 1990 by in situ hybridisation and it is localised on 17q11.2-q12 chromosome. It is also known as RANTES. RANTES was first described by Dr. Tom Schall who named the protein, the original source of the name Rantes was from the Argentine movie Man Facing Southeast about an alien who shows up in a mental ward who was named Rantés, the rather clunky acronym was only made to fit the name.
Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1α and MIP-1β that are now officially named CCL3 and CCL4, respectively. However, other names can sometimes be encountered, especially in older literature, as LD78α, AT 464.1 and GOS19-1 for human CCL3 and AT 744, Act-2, LAG-1, HC21 and G-26 for human CCL4. Other macrophage inflammatory proteins include MIP-2, MIP-3 and MIP-5.
Chemokine ligands 4 previously known as macrophage inflammatory protein (MIP-1β), is a protein which in humans is encoded by the CCL4 gene. CCL4 belongs to a cluster of genes located on 17q11-q21 of the chromosomal region. Identification and localization of the gene on the chromosome 17 was in 1990 although the discovery of MIP-1 was initiated in 1988 with the purification of a protein doublet corresponding to inflammatory activity from supernatant of endotoxinstimulated murine macrophages. At that time, it was also named as "macrophage inflammatory protein-1" (MIP-1) due to its inflammatory properties.
Chemokine ligand 1 (CCL1) is also known as small inducible cytokine A1 and I-309 in humans. CCL1 is a small glycoprotein that belongs to the CC chemokine family.
Chemokine ligand 7 (CCL7) is a small cytokine that was previously called monocyte-chemotactic protein 3 (MCP3). CCL7 is a small protein that belongs to the CC chemokine family and is most closely related to CCL2.
Chemokine ligand 8 (CCL8), also known as monocyte chemoattractant protein 2 (MCP2), is a protein that in humans is encoded by the CCL8 gene.
C-C motif chemokine 11 also known as eosinophil chemotactic protein and eotaxin-1 is a protein that in humans is encoded by the CCL11 gene. This gene is encoded on three exons and is located on chromosome 17.
Chemokine ligand 18 (CCL18) is a small cytokine belonging to the CC chemokine family. The functions of CCL18 have been well studied in laboratory settings, however the physiological effects of the molecule in living organisms have been difficult to characterize because there is no similar protein in rodents that can be studied. The receptor for CCL18 has been identified in humans only recently, which will help scientists understand the molecule's role in the body.
Chemokine ligand 15 (CCL15) is a small cytokine belonging to the CC chemokine family that is also known as leukotactin-1, MIP5 and HCC-2. CCL15 is expressed in liver, small intestine, colon, and in certain leukocytes and macrophages of the lung. It is chemotactic for neutrophils, monocytes, and lymphocytes and elicits its effects by binding to cell surface chemokine receptors like CCR1 and CCR3. The human CCL15 gene spans four exons and is located in a head-to-tail orientation on chromosome 17 with the gene of another CC chemokine known as CCL14.
Chemokine ligand 16 (CCL16) is a small cytokine belonging to the CC chemokine family that is known under several pseudonyms, including Liver-expressed chemokine (LEC) and Monotactin-1 (MTN-1). This chemokine is expressed by the liver, thymus, and spleen and is chemoattractive for monocytes and lymphocytes. Cellular expression of CCL16 can be strongly induced in monocytes by IL-10, IFN-γ and bacterial lipopolysaccharide. Its gene is located on chromosome 17, in humans, among a cluster of other CC chemokines. CCL16 elicits its effects on cells by interacting with cell surface chemokine receptors such as CCR1, CCR2, CCR5 and CCR8.
C-C motif chemokine 22 is a protein that in humans is encoded by the CCL22 gene.
CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response. However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome. CCL17 has also been linked to autoimmune and allergic diseases.
Chemokine ligand 26 (CCL26) is a small cytokine belonging to the CC chemokine family that is also called Eotaxin-3, Macrophage inflammatory protein 4-alpha (MIP-4-alpha), Thymic stroma chemokine-1 (TSC-1), and IMAC. It is expressed by several tissues including heart, lung and ovary, and in endothelial cells that have been stimulated with the cytokine interleukin 4. CCL26 is chemotactic for eosinophils and basophils and elicits its effects by binding to the cell surface chemokine receptor CCR3. This gene for chemokine is located on human chromosome 7.
CC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins since they span the cell membrane seven times. To date, ten true members of the CC chemokine receptor subfamily have been described. These are named CCR1 to CCR10 according to the IUIS/WHO Subcommittee on Chemokine Nomenclature.
Chemokine ligand 12 (CCL12) is a small cytokine belonging to the CC chemokine family that has been described in mice. It is also known as monocyte chemotactic protein 5 (MCP-5) and, due to its similarity with the human chemokine MCP-1, sometimes it is called MCP-1-related chemokine. CCL12 specifically attracts eosinophils, monocytes and lymphocytes. This chemokine is found predominantly in lymph nodes and thymus under normal conditions, and its expression can be hugely induced in macrophages. It is thought to coordinate cell movements during early allergic reactions, and immune response to pathogens. The gene for CCL12 is found in a cluster of CC chemokines on mouse chromosome 11.
C-C chemokine receptor type 2 (CCR2 or CD192 is a protein that in humans is encoded by the CCR2 gene. CCR2 is a CC chemokine receptor.
C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.
C-C chemokine receptor type 3 is a protein that in humans is encoded by the CCR3 gene.
References
- ↑ Garcia-Zepeda EA, et al.. Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and no allergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3. J Immunol. 1996;157:5613–5626
- ↑ Naruse et al., A YAC contig of the human CC chemokine genes clustered on chromosome 17q11.2. Genomics. 1996, 34(2):236-40.
- ↑ Blanpain et al., CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist. Blood. 1999, 94:1899-905.
- ↑ Lamkhioued et al., Monocyte chemoattractant protein (MCP)-4 expression in the airways of patients with asthma. Induction in epithelial cells and mononuclear cells by proinflammatory cytokines. Am J Respir Crit Care Med. 2000, 162:723-32.
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