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Gene Review

MADCAM1  -  mucosal vascular addressin cell adhesion...

Homo sapiens

Synonyms: MACAM1, MAdCAM-1, Mucosal addressin cell adhesion molecule 1, hMAdCAM-1
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Disease relevance of MADCAM1


Psychiatry related information on MADCAM1

  • Because nothing is known about these addressins during human development, we studied the expression and function of MAdCAM-1 (and PNAd for comparison) in fetuses and children [5].

High impact information on MADCAM1

  • The majority of transduced CD4(+) cells had a gut-homing potential because they expressed the mucosal integrin alpha4beta7, and displayed efficient binding to MAdCAM-1-expressing cells in vitro [6].
  • In utero MAdCAM-1 functionally governs lymphocyte adhesion to vessels both in the gut and PLNs by binding to alpha4beta7 integrin [5].
  • In utero and during early childhood, the mucosal addressin MAdCAM-1 plays a dominant role in lymphocyte-endothelial cell adhesion at mucosal and nonmucosal sites [5].
  • Immune cell trafficking in uterus and early life is dominated by the mucosal addressin MAdCAM-1 in humans [5].
  • According to the current paradigm of lymphocyte trafficking, primed B and T cells extravasate in the intestinal lamina propria chiefly by means of the mucosal homing receptor alpha4beta7, which interacts with the vascular addressin MAdCAM-1 [7].

Chemical compound and disease context of MADCAM1


Biological context of MADCAM1


Anatomical context of MADCAM1

  • Semiquantitative score of immunostaining intensity in the endometrial endothelium for MADCAM1 was highest in the late secretory phase, whereas that for CSPG2 peaked throughout the secretory phase [12].
  • The integrin alpha(4)beta(7) is the cell adhesion receptor for the mucosal vascular addressin MAdCAM-1, and this interaction is dominant in lymphocyte homing to Peyer's patch high endothelial venules, and plays key roles in lymphocyte recruitment at sites of inflammation [9].
  • MAdCAM-1 located on endothelial cells regulates this trafficking [10].
  • Decreased MAdCAM-1 expression occurred within hours of starting PN in Peyer's patches, but not mesenteric lymph nodes or the intestine, and recovered quickly with enteral refeeding [10].
  • OBJECTIVE: To determine the influence of route of nutrition on gut mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) expression and the effect of MAdCAM-1 blockade on gut-associated lymphoid tissue (GALT) lymphocyte populations and established respiratory antibacterial immunity [10].

Associations of MADCAM1 with chemical compounds

  • Mg(2+) promoted firm adhesion of alpha4beta7-expressing cells on MAdCAM-1 but with much lower tethering efficiency in shear flow [13].
  • A novel series of pyridazinone-functionalized phenylalanine analogues was prepared and evaluated for inhibition of cellular adhesion mediated by alpha4beta1/VCAM-1 and alpha4beta7/MAdCAM-1 interactions [14].
  • By contrast to results in Ca(2+) or Ca(2+) + Mg(2+), in Mg(2+) the alpha4beta7-MAdCAM-1 k(off) degrees decreased 20-fold to 0.046 s(-1), and the bond was weaker, providing an explanation for the finding of firm adhesion under these conditions [13].
  • Human MAdCAM-1 has a unique dual function compared to other members in the same subclass in that it binds both the integrin alpha4beta7, through its two IgSF domains, and a selectin expressed on leukocytes, via carbohydrate sidechains [15].
  • Secondly, architectural differences in the CD loops of MAdCAM-1 and VCAM-1 cause an 8 A shift in position of the critical aspartate residue, and may partly determine their binding preference for different integrins [15].

Physical interactions of MADCAM1


Regulatory relationships of MADCAM1


Other interactions of MADCAM1


Analytical, diagnostic and therapeutic context of MADCAM1


  1. Analysis of MAdCAM-1 and ICAM-1 polymorphisms in 365 Scandinavian patients with primary sclerosing cholangitis. Bowlus, C.L., Karlsen, T.H., Broom??, U., Thorsby, E., Vatn, M., Schrumpf, E., Lie, B.A., Boberg, K.M. J. Hepatol. (2006) [Pubmed]
  2. Loss of expression of alpha4beta7 integrin and L-selectin is associated with high-grade progression of low-grade MALT lymphoma. Liu, Y.X., Yoshino, T., Ohara, N., Oka, T., Jin, Z.S., Hayashi, K., Akagi, T. Mod. Pathol. (2001) [Pubmed]
  3. Genomic organization, chromosomal mapping, and analysis of the 5' promoter region of the human MAdCAM-1 gene. Leung, E., Berg, R.W., Langley, R., Greene, J., Raymond, L.A., Augustus, M., Ni, J., Carter, K.C., Spurr, N., Choo, K.H., Krissansen, G.W. Immunogenetics (1997) [Pubmed]
  4. Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease. Arihiro, S., Ohtani, H., Suzuki, M., Murata, M., Ejima, C., Oki, M., Kinouchi, Y., Fukushima, K., Sasaki, I., Nakamura, S., Matsumoto, T., Torii, A., Toda, G., Nagura, H. Pathol. Int. (2002) [Pubmed]
  5. Immune cell trafficking in uterus and early life is dominated by the mucosal addressin MAdCAM-1 in humans. Salmi, M., Alanen, K., Grenman, S., Briskin, M., Butcher, E.C., Jalkanen, S. Gastroenterology (2001) [Pubmed]
  6. Generation of regulatory gut-homing human T lymphocytes using ex vivo interleukin 10 gene transfer. Van Montfrans, C., Hooijberg, E., Rodriguez Pena, M.S., De Jong, E.C., Spits, H., Te Velde, A.A., Van Deventer, S.J. Gastroenterology (2002) [Pubmed]
  7. Regional specialization in the mucosal immune system: primed cells do not always home along the same track. Brandtzaeg, P., Farstad, I.N., Haraldsen, G. Immunol. Today (1999) [Pubmed]
  8. Antisense therapy of MAdCAM-1 for trinitrobenzenesulfonic acid-induced murine colitis. Goto, A., Arimura, Y., Shinomura, Y., Imai, K., Hinoda, Y. Inflamm. Bowel Dis. (2006) [Pubmed]
  9. The alpha(4) integrin subunit Tyr(187) has a key role in alpha(4)beta(7)-dependent cell adhesion. Ruiz-Velasco, N., Guerrero-Esteo, M., Briskin, M.J., Teixidó, J. J. Biol. Chem. (2000) [Pubmed]
  10. Enteral feeding preserves mucosal immunity despite in vivo MAdCAM-1 blockade of lymphocyte homing. Ikeda, S., Kudsk, K.A., Fukatsu, K., Johnson, C.D., Le, T., Reese, S., Zarzaur, B.L. Ann. Surg. (2003) [Pubmed]
  11. Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular endothelial cells. Ogawa, H., Binion, D.G., Heidemann, J., Theriot, M., Fisher, P.J., Johnson, N.A., Otterson, M.F., Rafiee, P. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  12. Potential selectin L ligands involved in selective recruitment of peripheral blood CD16(-) natural killer cells into human endometrium. Yamaguchi, T., Kitaya, K., Daikoku, N., Yasuo, T., Fushiki, S., Honjo, H. Biol. Reprod. (2006) [Pubmed]
  13. Kinetic and mechanical basis of rolling through an integrin and novel Ca2+-dependent rolling and Mg2+-dependent firm adhesion modalities for the alpha 4 beta 7-MAdCAM-1 interaction. de Château, M., Chen, S., Salas, A., Springer, T.A. Biochemistry (2001) [Pubmed]
  14. Synthesis and biological evaluation of novel pyridazinone-based alpha4 integrin receptor antagonists. Gong, Y., Barbay, J.K., Dyatkin, A.B., Miskowski, T.A., Kimball, E.S., Prouty, S.M., Fisher, M.C., Santulli, R.J., Schneider, C.R., Wallace, N.H., Ballentine, S.A., Hageman, W.E., Masucci, J.A., Maryanoff, B.E., Damiano, B.P., Andrade-Gordon, P., Hlasta, D.J., Hornby, P.J., He, W. J. Med. Chem. (2006) [Pubmed]
  15. The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important for integrin recognition. Tan, K., Casasnovas, J.M., Liu, J.H., Briskin, M.J., Springer, T.A., Wang, J.H. Structure (1998) [Pubmed]
  16. Novel modified tripeptide inhibitors of alpha 4 beta 7 mediated lymphoid cell adhesion to MAdCAM-1. Shroff, H.N., Schwender, C.F., Baxter, A.D., Brookfield, F., Payne, L.J., Cochran, N.A., Gallant, D.L., Briskin, M.J. Bioorg. Med. Chem. Lett. (1998) [Pubmed]
  17. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Its binding motif for alpha 4 beta 7 and role in experimental colitis. Fong, S., Jones, S., Renz, M.E., Chiu, H.H., Ryan, A.M., Presta, L.G., Jackson, D. Immunol. Res. (1997) [Pubmed]
  18. Transfection of IL-10 expression vectors into endothelial cultures attenuates alpha4beta7-dependent lymphocyte adhesion mediated by MAdCAM-1. Sasaki, M., Jordan, P., Houghton, J., Meng, X., Itoh, M., Joh, T., Alexander, J.S. BMC gastroenterology [electronic resource]. (2003) [Pubmed]
  19. Counter-receptors on human basophils for endothelial cell adhesion molecules. Bochner, B.S., Sterbinsky, S.A., Briskin, M., Saini, S.S., MacGlashan, D.W. J. Immunol. (1996) [Pubmed]
  20. Expression of mucosal addressin cell adhesion molecule 1 on vascular endothelium of gastric mucosa in patients with nodular gastritis. Ohara, H., Isomoto, H., Wen, C.Y., Ejima, C., Murata, M., Miyazaki, M., Takeshima, F., Mizuta, Y., Murata, I., Koji, T., Nagura, H., Kohno, S. World J. Gastroenterol. (2003) [Pubmed]
  21. The microenvironment of human Peyer's patches inhibits the increase in CD38 expression associated with the germinal center reaction. Guilliano, M.J., Foxx-Orenstein, A.E., Lebman, D.A. J. Immunol. (2001) [Pubmed]
  22. Elevated mucosal addressin cell adhesion molecule-1 expression in acquired immunodeficiency syndrome is maintained during antiretroviral therapy by intestinal pathogens and coincides with increased duodenal CD4 T cell densities. Miao, Y.M., Hayes, P.J., Gotch, F.M., Barrett, M.C., Francis, N.D., Gazzard, B.G. J. Infect. Dis. (2002) [Pubmed]
  23. Mucosal vaccination increases endothelial expression of mucosal addressin cell adhesion molecule 1 in the human gastrointestinal tract. Lindholm, C., Naylor, A., Johansson, E.L., Quiding-Järbrink, M. Infect. Immun. (2004) [Pubmed]
  24. Molecular cloning and characterization of pig, cow and sheep MAdCAM-1 cDNA and the demonstration of cross-reactive epitopes amongst mammalian homologuesdagger. Tachedjian, M., Yu, M., Lew, A.M., Rockman, S., Boyle, J.S., Andrew, M.E., Wang, L. Tissue Antigens (2006) [Pubmed]
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