Role of MAdCAM-1-Expressing High Endothelial Venule-Like Vessels in Colitis Induced in Mice Lacking Sulfotransferases Catalyzing L-Selectin Ligand Biosynthesis

• Published in: The journal of histochemistry and cytochemistry 2018-06, Vol.66 (6), p.415-425
• Main Authors: Low, Shulin, Hirakawa, Jotaro, Hoshino, Hitomi, Uchimura, Kenji, Kawashima, Hiroto, Kobayashi, Motohiro
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry, Molecular Biology; Carbohydrate Sulfotransferases; Cell Adhesion Molecules - analysis; Colitis, Ulcerative - genetics; Colitis, Ulcerative - pathology; Colon - blood supply; Colon - pathology; Disease Models, Animal; Gene Deletion; Human health and pathology; Immunohistochemistry; Intestinal Mucosa - blood supply; Intestinal Mucosa - pathology; L-Selectin - analysis; Life Sciences; Male; Mice, Inbred C57BL; Mice, Knockout; Mucoproteins; Oligosaccharides - analysis; Sialyl Lewis X Antigen; Sulfotransferases - genetics; Tissues and Organs; Venules - metabolism; Venules - pathology
• ISSN: 0022-1554; 1551-5044
• DOI: 10.1369/0022155417753363

Ulcerative colitis (UC) is a chronic inflammatory disease histologically characterized by diffuse mononuclear cell infiltrates in colonic mucosa. These inflammatory cells are considered to be recruited via high endothelial venule (HEV)-like vessels displaying mucosal addressin cell adhesion molecule 1 (MAdCAM-1), the ligand for α4β7 integrin, and/or peripheral lymph node addressin (PNAd), an L-selectin ligand. 6-O-sulfation of N-acetylglucosamine in the carbohydrate moiety of PNAd is catalyzed exclusively by N-acetylglucosamine-6-O-sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2. To determine the role of 6-O-sulfation of N-acetylglucosamine on HEV-like vessels in UC, we used a chronic dextran sulfate sodium–induced colitis model using mice deficient in both GlcNAc6ST-1 and GlcNAc6ST-2. We found that more inflammatory cells, with expression of tumor necrosis factor α, were infiltrated in double knockout mouse colitis compared with that in wild-type mice. Moreover, the number of MAdCAM-1-positive vessels was increased in double knockout mouse colitis, and these vessels were bound by E-selectin•IgM chimeras that bind to unsulfated sialyl Lewis X (sLeX). These findings suggest that interactions between MAdCAM-1 and α4β7 integrin and/or unsulfated sLeX and L-selectin may become a dominant mechanism for inflammatory cell recruitment in the absence of 6-sulfo sLeX and contribute to more severe colitis phenotypes seen in double knockout mice.