title: Inflammatory responses increase secretion of MD-1 protein.
abstract: Radioprotective 105 (RP105) is a type I transmembrane protein, which associates with a glycoprotein, MD-1. Monoclonal antibody (mAb)-mediated ligation of RP105/MD-1 robustly activates B cells. RP105/MD-1 is structurally similar to Toll-like receptor 4 (TLR4)/MD-2. B-cell responses to TLR2 and TLR4/MD-2 ligands are impaired in the absence of RP105 or MD-1. In addition to RP105/MD-1, MD-1 alone is secreted. The structure of MD-1 shows that MD-1 has a hydrophobic cavity that directly binds to phospholipids. Little is known, however, about a ligand for MD-1 and the role of MD-1 in vivo To study the role of RP105/MD-1 and MD-1 alone, specific mAbs against MD-1 are needed. Here, we report the establishment and characterization of two anti-MD-1 mAbs (JR2G9, JR7G1). JR2G9 detects soluble MD-1, whereas JR7G1 binds both soluble MD-1 and the cell surface RP105/MD-1 complex. With these mAbs, soluble MD-1 was detected in the serum and urine. The MD-1 concentration was altered by infection, diet and reperfusion injury. Serum MD-1 was rapidly elevated by TLR ligand injection in mice. The quantitative PCR and supernatant-precipitated data indicate that macrophages are one of the sources of serum soluble MD-1. These results suggest that soluble MD-1 is a valuable biomarker for inflammatory diseases.
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Richard
authors.initials: R
authors.lastname: Thomas Jennings
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
authors.forename: Erdenezaya
authors.initials: E
authors.lastname: Odkhuu
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
authors.forename: Akina
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Morita
authors.affiliation: Department of Molecular Immunology and Inflammation, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjyuku-ku, Tokyo 162-8655, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yamai
authors.affiliation: Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.affiliation: Laboratory of Molecular and Functional Bio-imaging, Faculty of Health Sciences, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Haga
authors.affiliation: Laboratory of Molecular and Functional Bio-imaging, Faculty of Health Sciences, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630, Toyama 930-0194, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630, Toyama 930-0194, Japan JST, PRESTO, 4-1-8, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630, Toyama 930-0194, Japan Toyama Prefectural Institute for Pharmaceutical Research, 17-1, Irimizu, Toyama 939-0363, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Teikyo University, 2-11-1, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Takane
authors.initials: T
authors.lastname: Kikuchi-Ueda
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Ichimonji
authors.affiliation: Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Bunkyo-ku, Tokyo 113-8510, Japan AMED, CREST, 1-7-1, Chiyoda-ku, Tokyo 100-0004, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan sachiko@aichi-med-u.ac.jp.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Akashi-Takamura
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD / Q000276:immunology; D000954:Antigens, Surface / Q000097:blood / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007249:Inflammation / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; C490500:Ly78 protein, mouse; C113553:Ly86 protein, mouse; D008562:Membrane Glycoproteins; D003907:Dexamethasone
keywords: MD-1; RP105; monoclonal antibody