Stage-specific expression of mucosal addressin cell adhesion molecule-1 during embryogenesis in rats.
Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is essential for lymphocyte trafficking to gut-associated lymphoid tissues and is implicated in inflammatory disorders in the gut and pancreatic islets. In this study, we examined the functional role of MAdCAM-1 during rat ontogeny using newly generated specific mAb. As previously observed in mice and humans, MAdCAM-1 was preferentially expressed in high endothelial venules (HEV) in gut-associated lymphoid tissues and venules of lamina propria in adult rats. Lymphocyte rolling and adhesion on HEV in Peyer's patches (PP) were completely abrogated with neutralizing anti-MAdCAM-1 mAb, in agreement with the notion that MAdCAM-1 is the principal HEV ligand for lymphocyte rolling and adhesion in adult PP. In the developing gastrointestinal tract, MAdCAM-1 was widely expressed in the venules of the lamina propria of fetal rats. In addition, MAdCAM-1 was also expressed in follicular dendritic cells in the neonatal PP. Interestingly, MAdCAM-1 expression was found also in nonmucosal tissues during ontogeny. MAdCAM-1 was transiently expressed in blood vascular endothelial cells in the fetal skin and neonatal thymus. Notably, MAdCAM-1-positive blood vessels were localized mainly in the cortico-medullary junction in the neonatal thymus and about 10-20% of thymocytes, most of which were either CD4, CD8 double positive or single positive specifically reacted with soluble MAdCAM-1 via integrin alpha4beta7. After birth, MAdCAM-1 expression in thymus blood vessels disappeared and concomitantly, the soluble MAdCAM-1-reactive thymocytes were rapidly down-regulated. Our results suggest that MAdCAM-1 functions as a vascular addressin in not only mucosal, but also nonmucosal lymphoid tissues during ontogeny.
Iizuka
T
T
Department of Bioregulation, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka, Japan.
Tanaka
T
T
Suematsu
M
M
Miura
S
S
Watanabe
T
T
Koike
R
R
Ishimura
Y
Y
Ishii
H
H
Miyasaka
N
N
Miyasaka
M
M
D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D000918:Antibody Specificity; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000276:immunology; D005314:Embryonic and Fetal Development / Q000276:immunology*; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000276:immunology; D007413:Intestinal Mucosa / Q000254:growth & development / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins / Q000096:biosynthesis* / Q000276:immunology; D010581:Peyer's Patches / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; C504268:Madcam1 protein, rat; D009088:Mucoproteins