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Addressin

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(Redirected from MadCAM1)

MADCAM1
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesMADCAM1, MACAM1, mucosal vascular addressin cell adhesion molecule 1
External IDsOMIM: 102670; GeneCards: MADCAM1; OMA:MADCAM1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

8174

n/a

Ensembl

ENSG00000099866

n/a

UniProt

Q13477

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RefSeq (mRNA)

NM_130762
NM_130760

n/a

RefSeq (protein)

NP_570116
NP_570118

n/a

Location (UCSC)Chr 19: 0.49 – 0.51 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is a protein that in humans is encoded by the MADCAM1 gene.[3][4][5] The protein encoded by this gene is an endothelial cell adhesion molecule that interacts preferentially with the leukocyte beta7 integrin LPAM-1 (alpha4 / beta7), L-selectin, and VLA-4 (alpha4 / beta1) on myeloid cells to direct leukocytes into mucosal and inflamed tissues. It is a member of the immunoglobulin superfamily and is similar to ICAM-1 and VCAM-1.[3]

Nomenclature

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Addressin is a lesser-used term to describe the group of adhesion molecules that are involved with lymphocyte homing, commonly found at high-endothelial venules (HEVs) where lymphocytes exit the blood and enter the lymph node.[6][7] Addressins are the ligands to the homing receptors of lymphocytes.[8] The task of these ligands and their receptors is to determine which tissue the lymphocyte will enter next. They carry carbohydrates in order to be recognized by L-selectin.[9] Addressins physically bind to mobile lymphocytes to guide them to the HEVs.[6] Examples of molecules that are often referred to as addressins are CD34 and GlyCAM-1 on HEVs in peripheral lymph nodes, and MAdCAM-1 on endothelial cells in the intestine.[7]

Function

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In terms of migration, MAdCAM-1 is selectively expressed on mucosal endothelial cells, driving memory T-cell re-circulation through mucosal tissues. In contrast, and indeed the main difference between the two molecules, ICAM molecules are involved with naïve T-cell re-circulation. Whereas MAdCAM-1 is selectively expressed, ICAM is broadly expressed on inflamed endothelium.

Peripheral node addressins

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Peripheral node addressins (PNAd) are carbohydrate residues that are lymphocyte homing receptor ligands that are expressed on the HEVs of peripheral lymph nodes.[10] These proteins collectively bind to L-selectin to guide lymphocytes such as mature naïve B and T cells into the lymph node.[9][11][12] During the development of secondary lymphoid organs, PNAd expression is upregulated following the upregulation and subsequent downregulation of MAdCAM-1 on HEVs.[12] PNAd expression, as well as the expression of MAdCAM-1, is dependent on lymphotoxin signaling in the HEVs of lymph nodes.[12]

Clinical significance

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In inflammatory bowel diseases, MAdCAM-1 can be overexpressed on the endothelial cells of intestinal mucosa and gut-associated lymphoid tissue, leading to excessive inflammation in the gut.[13] A potential therapeutic target to manage these diseases could be the MAdCAM-1 molecules that are expressed on these cells and bring in lymphocytes. One example of a potential therapy is the fully human monoclonal antibody ontamalimab that targets and binds to MAdCAM-1, preventing it from interacting with the integrins on the surface of the lymphocytes.[14]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000099866 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b "Entrez Gene: mucosal vascular addressin cell adhesion molecule 1".
  4. ^ Shyjan AM, Bertagnolli M, Kenney CJ, Briskin MJ (April 1996). "Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) demonstrates structural and functional similarities to the alpha 4 beta 7-integrin binding domains of murine MAdCAM-1, but extreme divergence of mucin-like sequences". Journal of Immunology. 156 (8): 2851–7. doi:10.4049/jimmunol.156.8.2851. PMID 8609404. S2CID 24940438.
  5. ^ Leung E, Berg RW, Langley R, Greene J, Raymond LA, Augustus M, et al. (1997). "Genomic organization, chromosomal mapping, and analysis of the 5' promoter region of the human MAdCAM-1 gene". Immunogenetics. 46 (2): 111–9. doi:10.1007/s002510050249. PMID 9162097. S2CID 9453114.
  6. ^ a b Bevilacqua MP (1993-04-01). "Endothelial-leukocyte adhesion molecules". Annual Review of Immunology. 11 (1): 767–804. doi:10.1146/annurev.iy.11.040193.004003. PMID 8476577.
  7. ^ a b Punt J (2019). Kuby immunology. Sharon A. Stranford, Patricia P. Jones, Judith A. Owen (Eighth ed.). New York. ISBN 978-1-4641-8978-4. OCLC 1002672752.{{cite book}}: CS1 maint: location missing publisher (link)
  8. ^ Addressin Archived 2016-12-01 at the Wayback Machine at eMedicine Dictionary
  9. ^ a b Berg EL, Robinson MK, Warnock RA, Butcher EC (July 1991). "The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor". The Journal of Cell Biology. 114 (2): 343–9. doi:10.1083/jcb.114.2.343. PMC 2289069. PMID 1712790.
  10. ^ Picker LJ, Butcher EC (1992-04-01). "Physiological and molecular mechanisms of lymphocyte homing". Annual Review of Immunology. 10 (1): 561–91. doi:10.1146/annurev.iy.10.040192.003021. PMID 1590996.
  11. ^ Lechleitner S, Kunstfeld R, Messeritsch-Fanta C, Wolff K, Petzelbauer P (September 1999). "Peripheral lymph node addressins are expressed on skin endothelial cells". The Journal of Investigative Dermatology. 113 (3): 410–4. doi:10.1046/j.1523-1747.1999.00696.x. PMID 10469342.
  12. ^ a b c Randall TD, Carragher DM, Rangel-Moreno J (2008-03-27). "Development of secondary lymphoid organs". Annual Review of Immunology. 26 (1): 627–50. doi:10.1146/annurev.immunol.26.021607.090257. PMC 2590644. PMID 18370924.
  13. ^ Arihiro S, Ohtani H, Suzuki M, Murata M, Ejima C, Oki M, et al. (2002). "Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease". Pathology International. 52 (5–6): 367–74. doi:10.1046/j.1440-1827.2002.01365.x. PMID 12100519. S2CID 38219521.
  14. ^ Picardo S, Panaccione R (April 2020). "Anti-MADCAM therapy for ulcerative colitis". Expert Opinion on Biological Therapy. 20 (4): 437–442. doi:10.1080/14712598.2020.1691520. PMID 31709847. S2CID 207946274.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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