title: Impaired selectin-ligand biosynthesis and reduced inflammatory responses in beta-1,4-galactosyltransferase-I-deficient mice.
abstract: Selectins recognize ligands containing carbohydrate chains such as sialyl Lewis x (sLex) that are mainly presented at the terminus of N-acetyl lactosamine repeats on core 2 O-glycans. Several glycosyltransferases act successively to extend the N-acetyl lactosamine repeats and to synthesize sLex, and beta-1,4-galactosyltransferase (beta4GalT) plays a key role in these processes. Recently isolated 6 beta4GalT genes are candidates, but their individual roles, including those in selectin-ligand biosynthesis, remain to be elucidated. More than 80% of the core 2 O-glycans on the leukocyte membrane glycoproteins of beta4GalT-I-deficient mice lacked galactose residues in beta-1,4 linkage, and soluble P-selectin binding to neutrophils and monocytes of these mice was significantly reduced, indicating an impairment of selectin-ligand biosynthesis. beta4GalT-I-deficient mice exhibited blood leukocytosis but normal lymphocyte homing to peripheral lymph nodes. Acute and chronic inflammatory responses, including the contact hypersensitivity (CHS) and delayed-type hypersensitivity (DTH) responses, were suppressed, and neutrophil infiltration into inflammatory sites was largely reduced in these mice. Our results demonstrate that beta4GalT-I is a major galactosyltransferase responsible for selectin-ligand biosynthesis and that inflammatory responses of beta4GalT-I-deficient mice are impaired because of the defect in selectin-ligand biosynthesis.
authors.affiliation: Department of Transgenic Animal Science, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8640, Japan. asano@kiea.m.kanazawa-u.ac.jp
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kotani
authors.forename: Naoki
authors.initials: N
authors.lastname: Shirafuji
authors.forename: Aya
authors.initials: A
authors.lastname: Nambu
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kawashima
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hirose
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takasaki
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003877:Dermatitis, Contact / Q000276:immunology / Q000378:metabolism*; D005700:Galactosyltransferases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism*; D007964:Leukocytosis / Q000503:physiopathology; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D011134:Polysaccharides / Q000096:biosynthesis / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D019087:Selectins / Q000378:metabolism*
chemical_list: D008024:Ligands; D011134:Polysaccharides; D019087:Selectins; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I