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

8174

n/a

Ensembl

ENSG00000099866

n/a

UniProt

Q13477

n/a

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

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

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

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

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000099866 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. 1 2 "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. 1 2 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. 1 2 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. 1 2 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. 1 2 3 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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