The mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a cell-surface Ig
superfamily member composed of two extracellular Ig domains, followed by a mucin-like
domain, a transmembrane domain and a short cytoplasmatic domain. It interacts via its Nterminal
Ig domain with the lymphocyte homing receptor integrin alpha4beta7. MAdCAM-1
promotes the adhesion of T and B cells, monocytes/macrophages, and potentially
eosinophils, basophils, and differentiated mast cells to the vascular endothelium and is
critical for lymphocyte homing to the gut. RNA transcripts are predominantly expressed in the
small intestine, mesenteric lymph nodes, colon and spleen. MAdCAM-1 transcripts are
weakly expressed in human pancreas and brain. The MAdCAM-1 protein (60 kDa) is widely
expressed on endothelia in both lymphoid and non-lymphoid tissues. Furthermore, it is
expressed in thymic medulla and on high endothelial venules (HEV). This expression
increases upon response to several cytokines including TNF-alpha, IL1b and IFN-gamma.
MAdCAM-1 expression is upregulated on HEV-like vessels in a variety of chronic
inflammatory diseases, and may mediate increased leukocyte trafficking into inflamed tissue.
In utero and during early childhood, MAdCAM-1 plays a dominant role in lymphocyteendothelial
cell adhesion at both mucosal and nonmucosal sites. In contrast, in the adult the
expression of MAdCAM-1 is restricted to mucosal tissues and has been shown to be
dramatically up-regulated during intestinal inflammation. In the gut, MADCAM-1 is basically
expressed on follicular dendrites in Peyer’s patches. Its expression is dramatically increased
in inflammatory bowel disease (IBD). It is expressed in animal models of IBD and in human
tissue samples from patients with Crohn’s disease and ulcerative colitis. MAdCAM-1 is
strongly expressed in the synovium of osteoarthritis patients, predominantly on the
endothelial lining of blood vessels, but also within the vessel lumen. The MAdCAM-1/integrin
alpha4beta7 homing system possibly participates in gastric inflammation in response to
Helicobacter pylori infection and contributes to mucosa-associated lymphoid tissue (MALT)
formation typically leading to the development of nodular gastritis.
Higher expression of MAdCAM-1 is reflected in elevated levels of the circulating soluble form
of MAdCAM-1 (sMAdCAM-1). Since MAdCAM-1 is elevated in inflammatory, infectious and
malignant diseases, sMAdCAM-1 serves as a perfect non-invasive biomarker for disease
acitivity. In sera of healthy donor, sMAdCAM-1 was detected at 236.5 ± 55.8 ng/ml. In urine
of healthy donors, sMAdCAM-1 was detected at 20-123 ng/ml. Measurement of sMAdCAM-1
levels is potentially useful to monitor disease activity and the results of therapy.
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