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MADCAM1

Official Full Name
mucosal vascular addressin cell adhesion molecule 1
Background
The protein encoded by this gene is an endothelial cell adhesion molecule that interacts preferentially with the leukocyte beta7 integrin LPAM-1 (alpha4beta7), L-selectin, and VLA-4 (alpha4beta1) on myeloid cells to direct leukocytes into mucosal and inf
Synonyms
MADCAM1; mucosal vascular addressin cell adhesion molecule 1; mucosal addressin cell adhesion molecule 1; MACAM1; MAdCAM-1; hMAdCAM-1; mucosal addressin cell adhesion molecule-1

Mucosal vascular address cell adhesion molecule-1 (MAdCAM1) is an adhesion molecule belonging to the immunoglobulin superfamily and the mucin-like adhesion receptor family. MAdCAM1 is mainly expressed on the surface of vascular endothelial cells of the intestinal tract and its associated lymphoid tissue. It is recognized as a marker of intestinal mucosal tissue for the recognition of lymphocytes in the circulation and is involved in various physiological and pathological processes such as lymphocyte recycling and homing.

Figure 1. Blocking of immune cell trafficking to the colon. (Emiko, et al. 2013)

MADCAM1 Functions

Under normal conditions, MAdCAM-1 molecules are selectively expressed in Peyer's Patch (PP), high endothelial venules (HELVs) of mesenteric lymph nodes (MLN). It is also expressed on the surface of flat vascular endothelial cells in the lamina propria (LP) of the large and small intestine, and is rarely expressed in extraintestinal tissues.

Studies have shown that the interaction of vascular endothelial cells with lymphocytes is a critical step in the migration of lymphocytes from the bloodstream to surrounding tissues, involving the initial attachment, activation and adhesion of lymphocytes, and the cascade of endothelial cells. In this process, as a ligand for L-selectin and α4β7 molecules on lymphocytes, MAdCAM1 molecules are involved in L-selectin-mediated adherent rolling and α4β7-mediated activation and enhanced adhesion. In the lamina propria of the intestinal mucosa lacking L-selectin, only the interaction of α4β7/MAdCAM-1 can initiate the initial adhesion of lymphocytes. It is shown that MAdCAM-1 molecules have the ability to mediate lymphocytic extravasation into tissues. The interaction of the MAdCAM-1 molecule with the mucosal homing receptor α4β7 plays an important role in mediating the selective localization and recycling of lymphocytes to gut-associated lymphoid tissue (GALT).

MADCAM1 Is Involved in The Regulation of Inflammatory Responses

In experimental colitis in mice, immunohistochemical staining showed a large number of β7 + lymphocytes in the inflammation site. MAdCAM1+ blood vessels were also more abundant. Expression of MAdCAM1 molecules in the lamina propria, submucosa and serosal layer is significantly higher than the control group. In vivo application of MAdCAM1 and / or β7 monoclonal antibody can effectively block the exudation of lymphocytes to inflammatory tissues, the blocking rate is 72% to 98%, and the colonic lesions are also significantly reduced. Studies have shown that during chronic inflammation, MAdCAM1 molecules are involved in the inflammatory response by mediating circulating lymphocytes into the site of inflammation.

Proinflammatory mediators released by inflammatory cells, such as TNF-α, IFN-γ, IL-1 and LPS, can induce or regulate the expression of adhesion molecules such as MAdCAM1 and VCAM1 in vascular endothelial cells, and then promote A unique phenotypic memory lymphocyte infiltrates into the inflammatory tissue. Thus, the MAdCAM1 molecule is closely related to certain inflammatory diseases and plays an important role in its pathogenesis.

MADCAM1 and Disease

Clinically, autoimmune diseases such as rheumatoid disease and multiple sclerosis are associated with adhesion molecules. Animal experiments have also confirmed that chronic inflammatory diseases such as colitis and insulin-dependent diabetes mellitus (IDDM) are associated with abnormal expression of adhesion molecules such as MAdCAM1. Monoclonal antibodies against MAdCAM1 have been used in the treatment of chronic diseases mentioned above in animals and have achieved initial results. In addition to using monoclonal antibody to specifically seal the binding of adhesion receptors and ligands, soluble adhesion molecules and polypeptide molecules that mimic the binding sites of adhesion molecules or oral small-molecule oligosaccharide complexes can also be considered to block the adhesion of lymphocytes to EC.

References:

  1. Emiko, M. , Deanna, N. , & Daren, L. . (2013). Animal models of ulcerative colitis and their application in drug research. Drug Design, Development and Therapy, 1341-.
  2. Clahsen, T. , Pabst, O. , Tenbrock, K. , Schippers, A. , & Wagner, N. . (2015). Localization of dendritic cells in the gut epithelium requires madcam-1. Clinical Immunology, 156(1), 74-84.
  3. Drescher, H. K. , Schippers, A. , Erschfeld, S. , Noels, H. , Wagner, N. , & Trautwein, C. , et al. (2014). O28 β7-integrins and madcam-1 play an opposing role during the development of non-alcoholic steatohepatitis (nash). Journal of Hepatology,60(1), S12.

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