title: Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue.
abstract: Lymphocyte homing to normal tissues and recruitment to inflammatory tissue sites are controlled, in part, by the selective expression of chemokines, pro-inflammatory cytokines and mediators, and various adhesion proteins and molecules. In the mouse, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is selectively expressed on endothelium of high endothelial venules in gut and gut-associated lymphoid tissue. By interaction with its integrin ligand, alpha 4 beta 7, lymphocytes presumed to be involved in mucosal immunity are selectively recruited to these intestinal sites. After generating monoclonal antibodies against a murine cell line expressing recombinant human MAdCAM-1, we qualitatively and semiquantitatively assessed MAdCAM-1 expression in human tissue sections from various normal and inflammatory disorders. We found that human MAdCAM-1, as in the mouse, is expressed in a tissue-selective manner. In normal tissues, MAdCAM-1 is constitutively expressed to endothelium of venules of intestinal lamina propria. Interestingly, using computer-assisted morphometric analysis, the proportion of venular endothelium within lamina propria that expresses MAdCAM-1 is increased, compared with normal tissues, at inflammatory foci associated with ulcerative colitis and Crohn's disease. Moreover, for the most part, MAdCAM-1 is not detected in the majority of normal or inflamed extra-intestinal tissues, including those with mucosal surfaces. These results are consistent with a role, as originally defined in the mouse, for human MAdCAM-1 in the localization of alpha 4 beta 7+ lymphocytes in the gastrointestinal tract and associated lymphoid tissue. As such, the pathway defined by MAdCAM-1/alpha 4 beta 7 may be a relevant tissue-specific therapeutic target for the modulation of inflammatory bowel disease activity.
authors.affiliation: LeukoSite, Inc., Cambridge, Massachusetts 02142, USA.
authors.forename: M
authors.initials: M
authors.lastname: Briskin
authors.forename: D
authors.initials: D
authors.lastname: Winsor-Hines
authors.forename: A
authors.initials: A
authors.lastname: Shyjan
authors.forename: N
authors.initials: N
authors.lastname: Cochran
authors.forename: S
authors.initials: S
authors.lastname: Bloom
authors.forename: J
authors.initials: J
authors.lastname: Wilson
authors.forename: L M
authors.initials: LM
authors.lastname: McEvoy
authors.forename: E C
authors.initials: EC
authors.lastname: Butcher
authors.forename: N
authors.initials: N
authors.lastname: Kassam
authors.forename: C R
authors.initials: CR
authors.lastname: Mackay
authors.forename: W
authors.initials: W
authors.lastname: Newman
authors.forename: D J
authors.initials: DJ
authors.lastname: Ringler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D016466:CHO Cells; D015815:Cell Adhesion Molecules; D003106:Colon / Q000378:metabolism; D006224:Cricetinae; D003429:Cross Reactions; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology; D016393:Lymphoma, B-Cell; D008253:Macaca mulatta; D051379:Mice; D009088:Mucoproteins / Q000096:biosynthesis* / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis* / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D016201:Receptors, Lymphocyte Homing