Macrophage inflammatory protein

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chemokine (C-C motif) ligand 3
1b53.png
Human Mip-1α dimer D26A mutant. PDB 1b53.[1] Disulfide bonds highlighted.
Identifiers
SymbolCCL3
Alt. symbolsSCYA3, MIP-1α
NCBI gene6348
HGNC10627
OMIM182283
PDB1B50 More structures
RefSeqNM_002983
UniProtP10147
Other data
LocusChr. 17 q12
chemokine (C-C motif) ligand 4
1hum.png
Human Mip-1β dimer. PDB 1hum.[2] Disulfide bonds highlighted.
Identifiers
SymbolCCL4
Alt. symbolsSCYA4, MIP-1β, LAG1
NCBI gene6351
HGNC10630
OMIM182284
PDB1HUM More structures
RefSeqNM_002984
UniProtP13236
Other data
LocusChr. 17 q21-q23

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 (according to the new nomenclature) officially named CCL3 and CCL4, respectively.[3] But we can sometimes encounter other names, 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.[4] But there are other macrophage inflammatory proteins aside from MIP-1. Namely MIP-2, MIP-3 and MIP-5.

MIP-1[edit]

MIP-1α and MIP-1β are major factors produced by macrophages and monocytes after they are stimulated with bacterial endotoxin[5] or proinflammatory cytokines such as IL-1β.[4] But it appears that they can be expressed by all hematopoietic cells and some tissue cells such as fibroblasts, epithelial cells, vascular smooth muscle cells or platelets upon activation.[4] They are crucial for immune responses towards infection and inflammation.[6] CCL3 and CCL4 can bind to extracellular proteoglycans, which is not necessary for their function but it can enhance their bioactivity.[7] The biological effect is carried out through ligation of chemokine receptors CCR1 (ligand CCL3) and CCR5 (ligands CCL3 and CCL4) and the signal is then transferred into the cell, thus these cytokines effect any cell that has these receptors.[8] The main effect is inflammatory and mainly consists of chemotaxis and transendothelial migration but cells can be activated to release of some bioactive molecules also. These chemokines affect monocytes, T lymphocytes, dendritic cells, NK cells and platelets.[4] They, too, activate human granulocytes (neutrophils, eosinophils and basophils) which can lead to acute neutrophilic inflammation. They also induce the synthesis and release of other pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-α from fibroblasts and macrophages. The genes for CCL3 and CCL4 are both located on human chromosome 17[9] and on murine chromosome 11.[4]

They are produced by many cells, particularly macrophages, dendritic cells, and lymphocytes.[10] MIP-1 are best known for their chemotactic and proinflammatory effects but can also promote homeostasis.[10] Biophysical analyses and mathematical modelling has shown that MIP-1 reversibly forms a polydisperse distribution of rod-shaped polymers in solution. Polymerization buries receptor-binding sites of MIP-1, thus depolymerization mutations enhance MIP-1 to arrest monocytes onto activated human endothelium.[6]

MIP-1γ is another macrophage inflammatory protein and according to the new nomenclature is named CCL9.[3] It is produced mainly by follicle-associated epithelial cells and is responsible for chemotaxis of dendritic cells and macrophages into Peyer's patches in gut through binding of CCR1.[11]

MIP-1δ or MIP-5 (CCL15) binds also CCR1 and CCR3.[3]

MIP-2[edit]

MIP-2 belongs to the CXC chemokine family, is named CXCL2 and acts through binding of CXCR1 and CXCR2. It is produced mainly by macrophages, monocytes and epithelial cells and is responsible for chemotaxis to the source of inflammation and activation of neutrophils.[12]

MIP-3[edit]

There are two chemokines in the MIP-3 group. MIP-3α (CCL20) and MIP-3β (CCL19).[3]

MIP-3α is binding to receptor CCR6.[13] CCL20 is produced by mucosa and skin by activated epithelial cells and attracts Th17 cells to the site of inflammation. It is also produced by Th17 cells themselves.[14] It further attracts activated B cells, memory T cells and immature dendritic cells and has part in migration of these cells in secondary lymphoid organs.[15][16] Mature dendritic cells down-regulate CCR6 and up-regulate CCR7, which is receptor for MIP-3β.[15]

MIP-3β (CCL19) is produced by stromal cells in T-cell zones of secondary lymphoid organs and binds to CCR7 receptor through which attracts mature dendritic cells to lymph nodes. It is also produced by dendritic cells and attracts also naive T lymphocytes and B lymphocytes to homing into the lymph node, where antigens can be presented to them by dendritic cells.[17]

MIP-5[edit]

MIP-5 (sometimes called MIP-1δ) or CCL15 binds to receptors CCR1 and CCR3. It has chemotactic properties for monocytes and eosinophils and is expressed by macrophages, basophils and some tissue cells. It is proposed to have a role in pathology of asthma.[18]

See also[edit]

References[edit]

  1. ^ Czaplewski LG, McKeating J, Craven CJ, Higgins LD, Appay V, Brown A, et al. (June 1999). "Identification of amino acid residues critical for aggregation of human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES. Characterization of active disaggregated chemokine variants". The Journal of Biological Chemistry. 274 (23): 16077–84. doi:10.1074/jbc.274.23.16077. PMID 10347159.
  2. ^ Lodi PJ, Garrett DS, Kuszewski J, Tsang ML, Weatherbee JA, Leonard WJ, et al. (March 1994). "High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR". Science. 263 (5154): 1762–7. doi:10.1126/science.8134838. PMID 8134838.
  3. ^ a b c d Zlotnik A, Yoshie O (February 2000). "Chemokines: a new classification system and their role in immunity". Immunity. 12 (2): 121–7. doi:10.1016/S1074-7613(00)80165-X. PMID 10714678.
  4. ^ a b c d e Menten P, Wuyts A, Van Damme J (December 2002). "Macrophage inflammatory protein-1". Cytokine & Growth Factor Reviews. 13 (6): 455–81. doi:10.1016/S1359-6101(02)00045-X. PMID 12401480.
  5. ^ Sherry B, Tekamp-Olson P, Gallegos C, Bauer D, Davatelis G, Wolpe SD, et al. (December 1988). "Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta". The Journal of Experimental Medicine. 168 (6): 2251–9. doi:10.1084/jem.168.6.2251. PMC 2189160. PMID 3058856.
  6. ^ a b Ren M, Guo Q, Guo L, Lenz M, Qian F, Koenen RR, et al. (December 2010). "Polymerization of MIP-1 chemokine (CCL3 and CCL4) and clearance of MIP-1 by insulin-degrading enzyme". The EMBO Journal. 29 (23): 3952–66. doi:10.1038/emboj.2010.256. PMC 3020635. PMID 20959807.
  7. ^ Ali S, Palmer AC, Banerjee B, Fritchley SJ, Kirby JA (April 2000). "Examination of the function of RANTES, MIP-1alpha, and MIP-1beta following interaction with heparin-like glycosaminoglycans". The Journal of Biological Chemistry. 275 (16): 11721–7. doi:10.1074/jbc.275.16.11721. PMID 10766793.
  8. ^ Murphy K, Weaver C (2017). Janeway's Immunobiology. New York: Garland Science, Taylor & Francis Group, LLC. p. 456. ISBN 978-0-8153-4505-3.
  9. ^ Irving SG, Zipfel PF, Balke J, McBride OW, Morton CC, Burd PR, et al. (June 1990). "Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q". Nucleic Acids Research. 18 (11): 3261–70. doi:10.1093/nar/18.11.3261. PMC 330932. PMID 1972563.
  10. ^ a b Maurer M, von Stebut E (October 2004). "Macrophage inflammatory protein-1". The International Journal of Biochemistry & Cell Biology. 36 (10): 1882–6. doi:10.1016/j.biocel.2003.10.019. PMID 15203102.
  11. ^ Murphy, Kenneth; Weaver, Casey (2017). Janeway's Immunobiology. New York: Garland Science, Taylor & Francis Group, LLC. p. 499. ISBN 978-0-8153-4505-3.
  12. ^ Qin CC, Liu YN, Hu Y, Yang Y, Chen Z (May 2017). "Macrophage inflammatory protein-2 as mediator of inflammation in acute liver injury". World Journal of Gastroenterology. 23 (17): 3043–3052. doi:10.3748/wjg.v23.i17.3043. PMC 5423041. PMID 28533661.
  13. ^ Elhousiny M, Miller K, Ariyawadana A, Nimmo A (December 2019). "Identification of inflammatory mediators associated with metastasis of oral squamous cell carcinoma in experimental and clinical studies: systematic review". Clinical & Experimental Metastasis. 36 (6): 481–492. doi:10.1007/s10585-019-09994-x. PMID 31559586.
  14. ^ Murphy, Kenneth; Weaver, Casey (2017). Janeway's Immunobiology. New York: Garland Science, Taylor & Francis Group, LLC. p. 465. ISBN 978-0-8153-4505-3.
  15. ^ a b Caux C, Ait-Yahia S, Chemin K, de Bouteiller O, Dieu-Nosjean MC, Homey B, et al. (December 2000). "Dendritic cell biology and regulation of dendritic cell trafficking by chemokines". Springer Seminars in Immunopathology. 22 (4): 345–69. doi:10.1007/s002810000053. PMID 11155441.
  16. ^ Lee AY, Körner H (May 2019). "The CCR6-CCL20 axis in humoral immunity and T-B cell immunobiology". Immunobiology. 224 (3): 449–454. doi:10.1016/j.imbio.2019.01.005. PMID 30772094.
  17. ^ Yan Y, Chen R, Wang X, Hu K, Huang L, Lu M, Hu Q (2019-10-01). "CCL19 and CCR7 Expression, Signaling Pathways, and Adjuvant Functions in Viral Infection and Prevention". Frontiers in Cell and Developmental Biology. 7: 212. doi:10.3389/fcell.2019.00212. PMC 6781769. PMID 31632965.
  18. ^ Shimizu Y, Dobashi K (2012). "CC-chemokine CCL15 expression and possible implications for the pathogenesis of IgE-related severe asthma". Mediators of Inflammation. 2012: 475253. doi:10.1155/2012/475253. PMC 3508751. PMID 23258953.

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