Biology:Addressin

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is a protein that in humans is encoded by the MADCAM1 gene.[1][2][3] 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.[1]

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.[4][5] Addressins are the ligands to the homing receptors of lymphocytes.[6] 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.[7] Addressins physically bind to mobile lymphocytes to guide them to the HEVs.[4] 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.[5]

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.[8] These proteins collectively bind to L-selectin to guide lymphocytes such as mature naïve B and T cells into the lymph node.[7][9][10] During the development of secondary lymphoid organs, PNAd expression is upregulated following the upregulation and subsequent downregulation of MAdCAM-1 on HEVs.[10] PNAd expression, as well as the expression of MAdCAM-1, is dependent on lymphotoxin signaling in the HEVs of lymph nodes.[10]

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.[11] 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.[12]

See also

References

  1. ↑ 1.0 1.1 "Entrez Gene: mucosal vascular addressin cell adhesion molecule 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8174. 
  2. ↑ "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. April 1996. doi:10.4049/jimmunol.156.8.2851. PMID 8609404. 
  3. ↑ "Genomic organization, chromosomal mapping, and analysis of the 5' promoter region of the human MAdCAM-1 gene". Immunogenetics 46 (2): 111–9. 1997. doi:10.1007/s002510050249. PMID 9162097. 
  4. ↑ 4.0 4.1 "Endothelial-leukocyte adhesion molecules". Annual Review of Immunology 11 (1): 767–804. 1993-04-01. doi:10.1146/annurev.iy.11.040193.004003. PMID 8476577. 
  5. ↑ 5.0 5.1 Kuby immunology. Sharon A. Stranford, Patricia P. Jones, Judith A. Owen (Eighth ed.). New York. 2019. ISBN 978-1-4641-8978-4. OCLC 1002672752. 
  6. ↑ Addressin at eMedicine Dictionary
  7. ↑ 7.0 7.1 "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. July 1991. doi:10.1083/jcb.114.2.343. PMID 1712790. 
  8. ↑ "Physiological and molecular mechanisms of lymphocyte homing". Annual Review of Immunology 10 (1): 561–91. 1992-04-01. doi:10.1146/annurev.iy.10.040192.003021. PMID 1590996. 
  9. ↑ "Peripheral lymph node addressins are expressed on skin endothelial cells". The Journal of Investigative Dermatology 113 (3): 410–4. September 1999. doi:10.1046/j.1523-1747.1999.00696.x. PMID 10469342. 
  10. ↑ 10.0 10.1 10.2 "Development of secondary lymphoid organs". Annual Review of Immunology 26 (1): 627–50. 2008-03-27. doi:10.1146/annurev.immunol.26.021607.090257. PMID 18370924. 
  11. ↑ "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. 2002. doi:10.1046/j.1440-1827.2002.01365.x. PMID 12100519. 
  12. ↑ "Anti-MADCAM therapy for ulcerative colitis". Expert Opinion on Biological Therapy 20 (4): 437–442. April 2020. doi:10.1080/14712598.2020.1691520. PMID 31709847. 

Further reading

External links

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



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