Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''MADCAM1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The protein encoded by this gene is an

endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...

molecule that interacts preferentially with the leukocyte beta7 integrin LPAM-1 ( alpha4 / beta7),

L-selectin L-selectin, also known as CD62L, is a cell adhesion molecule found on the cell surface of leukocytes, and the blastocyst. It is coded for in the human by the ''SELL'' gene. L-selectin belongs to the selectin family of proteins, which recognize s ...

, and

VLA-4 Integrin α4β1 (very late antigen-4) is an integrin dimer. It is composed of CD49d (alpha 4) and CD29 (beta 1). The alpha 4 subunit is 155 kDa, and the beta 1 subunit is 150 kDa. Function The integrin VLA-4 is expressed on the cell surfaces ...

(alpha4 / beta1) on myeloid cells to direct

leukocyte White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

s into mucosal and inflamed tissues. It is a member of the

immunoglobulin superfamily The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily ba ...

and is similar to

ICAM-1 ICAM-1 (Intercellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) is a protein that in humans is encoded by the ''ICAM1'' gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial ...

and

VCAM-1 Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106) is a protein that in humans is encoded by the ''VCAM1'' gene. VCAM-1 functions as a cell adhesion molecule. Stru ...

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. Addressins are the

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

s to the homing receptors of

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

s. 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

. Addressins physically bind to mobile lymphocytes to guide them to the HEVs. Examples of molecules that are often referred to as addressins are

CD34 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...

and

GlyCAM-1 Glycosylation-dependent cell adhesion molecule-1 (GLYCAM1) is a proteoglycan ligand expressed on cells of the high endothelial venules in lymphoid tissues. It is the ligand for the receptor L-selectin L-selectin, also known as CD62L, is a cell ...

on HEVs in peripheral lymph nodes, and MAdCAM-1 on endothelial cells in the intestine.

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

lymphotoxin Lymphotoxin is a member of the tumor necrosis factor (TNF) superfamily of cytokines, whose members are responsible for regulating the growth and function of lymphocytes and are expressed by a wide variety of cells in the body. Lymphotoxin plays ...

signaling in the HEVs of lymph nodes.

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. 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 A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

ontamalimab that targets and binds to MAdCAM-1, preventing it from interacting with the integrins on the surface of the lymphocytes.

References

External links

* * * Proteins {{gene-19-stub