Human MAdCAM-1 APC-conjugated Antibody

Applications

Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website.

Preparation and Storage

Background: MAdCAM-1

Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) is an approximately 60 kDa type 1 transmembrane glycoprotein. It is an endothelial cell adhesion molecule that belongs to the immunoglobulin (Ig) superfamily of proteins (1). Human MAdCAM-1 is synthesized as a 382 amino acid (aa) precursor that contains an 18 aa signal sequence, a 299 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 44 aa cytoplasmic tail. Within the ECD there is one potential site for N-linked glycosylation (2). The ECD comprises two Ig-like domains of 90 aa and 119 aa, respectively, each possessing invariant cysteine residues that stabilize the Ig loop (2). There is also a Ser-Thr-Pro-rich (71%) mucin-like 48 aa domain that is (aa 206‑317) formed by six tandem repeats of an eight aa sequence having the general consensus DTTSPEP/SP. This mucin domain contains 19 potential sites for O-linked glycosylation (2, 3). A splicing variant in which a single Ala residue is substituted for aa 223‑334 in isoform 1 produces a second isoform. Human mature MAdCAM-1 shares only 44% aa sequence identity with mature mouse MAdCAM-1. The integrin alpha (4)  beta (7), which is expressed on lymphocytes, functions as the MAdCAM-1 receptor (1). The Ig domains of MAdCAM-1 are critical to alpha (4)  beta (7) binding, and the mucin domain has activity in L‑Selectin binding. MAdCAM-1 expression is up-regulated by TNF-alpha  and IL‑1 beta. MAdCAM-1 is expressed on the surface of High Endothelial Venules (HEV) in the gut and in Peyer’s patches, on endothelial cells of the mesenteric lymph nodes, lamina propria of the small and large intestine, and the mammary gland during lactation, and on brain endothelial cells (1). MAdCAM‑1 has also been reported to be expressed in the liver portal region in autoimmune hepatitis (1), and in bone marrow following allogenic (genetically non-identical) hematopoietic stem cell transplantation, where it recruits donor T cells, which may lead to graft versus host disease (3, 4). MAdCAM‑1 functions as a homing receptor, and plays a central role in leukocyte migration into HEVs and Peyer’s patch (5). In addition to its normal role in lymphocyte trafficking to mucosal tissue, MAdCAM‑1 expression is also dramatically increased in chronic inflammatory and disease states (1, 6), including inflammatory bowel disease (Crohn’s disease and ulcerative colitis) (7), sclerosing cholangitis (8), and diabetes (9), and may play an important role in these conditions.

Product Datasheets

Related Research Areas

• Adhesion Molecules in Angiogenesis
• Immunoglobulin Superfamily CAMs
• Regulatory T Cells (Tregs)