| First Author | Asano M | Year | 2003 |
| Journal | Blood | Volume | 102 |
| Issue | 5 | Pages | 1678-85 |
| PubMed ID | 12714507 | Mgi Jnum | J:106669 |
| Mgi Id | MGI:3619189 | Doi | 10.1182/blood-2003-03-0836 |
| Citation | Asano M, et al. (2003) Impaired selectin-ligand biosynthesis and reduced inflammatory responses in beta-1,4-galactosyltransferase-I-deficient mice. Blood 102(5):1678-85 |
| abstractText | 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. |
