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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2003-03-0836. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0836v1 102/5/1678    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Asano, M. Articles by Iwakura, Y. Search for Related Content PubMed PubMed Citation Articles by Asano, M. Articles by Iwakura, Y. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Phagocytes Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2003, Vol. 102, No. 5, pp. 1678-1685 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Impaired selectin-ligand biosynthesis and reduced inflammatory responses in -1,4-galactosyltransferase-I–deficient mice Masahide Asano, Susumu Nakae, Norihiro Kotani, Naoki Shirafuji, Aya Nambu, Noriyoshi Hashimoto, Hiroto Kawashima, Mayumi Hirose, Masayuki Miyasaka, Seiichi Takasaki, and Yoichiro Iwakura From the Department of Transgenic Animal Science, Graduate School of Medical Science, Kanazawa University; Center for Experimental Medicine, Department of Biochemistry, and Department of Advanced Medical Science, Institute of Medical Science, University of Tokyo; and Laboratory of Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, Japan. 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 -1,4-galactosyltransferase (4GalT) plays a key role in these processes. Recently isolated 6 4GalT 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 4GalT-I–deficient mice lacked galactose residues in -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. 4GalT-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 4GalT-I is a major galactosyltransferase responsible for selectin-ligand biosynthesis and that inflammatory responses of 4GalT-I–deficient mice are impaired because of the defect in selectin-ligand biosynthesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Nishie, O. Miyaishi, H. Azuma, A. Kameyama, C. Naruse, N. Hashimoto, H. Yokoyama, H. Narimatsu, T. Wada, and M. Asano Development of Immunoglobulin A Nephropathy- Like Disease in {beta}-1,4-Galactosyltransferase-I-Deficient Mice Am. J. Pathol., February 1, 2007; 170(2): 447 - 456. [Abstract] [Full Text] [PDF] S. A. Francis, X. Shen, J. B. Young, P. Kaul, and D. J. Lerner Rho GEF Lsc is required for normal polarization, migration, and adhesion of formyl-peptide-stimulated neutrophils Blood, February 15, 2006; 107(4): 1627 - 1635. [Abstract] [Full Text] [PDF] J. J. Garcia-Vallejo, W. van Dijk, I. van Die, and S. I. Gringhuis Tumor Necrosis Factor-{alpha} Up-regulates the Expression of {beta}1,4-Galactosyltransferase I in Primary Human Endothelial Cells by mRNA Stabilization J. Biol. Chem., April 1, 2005; 280(13): 12676 - 12682. [Abstract] [Full Text] [PDF] T. Koike, N. Kimura, K. Miyazaki, T. Yabuta, K. Kumamoto, S. Takenoshita, J. Chen, M. Kobayashi, M. Hosokawa, A. Taniguchi, et al. Hypoxia induces adhesion molecules on cancer cells: A missing link between Warburg effect and induction of selectin-ligand carbohydrates PNAS, May 25, 2004; 101(21): 8132 - 8137. [Abstract] [Full Text] [PDF] R. Mori, T. Kondo, T. Nishie, T. Ohshima, and M. Asano Impairment of Skin Wound Healing in {beta}-1,4-Galactosyltransferase-Deficient Mice with Reduced Leukocyte Recruitment Am. J. Pathol., April 1, 2004; 164(4): 1303 - 1314. [Abstract] [Full Text] [PDF]

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