1. Inflammatory responses increase secretion of MD-1 protein
- Author
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Toshihiko Kobayashi, Tatsuya Yamazaki, Richard Thomas Jennings, Miyako Tanaka, Isao Ichimonji, Akina Nakashima, Ikuko Yamai, Yoshinori Nagai, Hidekazu Takagi, Sanae Haga, Kensuke Miyake, Yoshihiro Ogawa, Naoko Morita, Takane Kikuchi-Ueda, Erdenezaya Odkhuu, Yasuharu Watanabe, Sachiko Akashi-Takamura, Takayoshi Suganami, Michitaka Ozaki, and Kiyoshi Takatsu
- Subjects
0301 basic medicine ,Male ,medicine.drug_class ,Immunology ,Mice, Transgenic ,Monoclonal antibody ,Dexamethasone ,Antigen-Antibody Reactions ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,Antigens, CD ,medicine ,Immunology and Allergy ,Animals ,Secretion ,Receptor ,chemistry.chemical_classification ,Inflammation ,Mice, Knockout ,Mice, Inbred BALB C ,Membrane Glycoproteins ,biology ,Cell Death ,Antibodies, Monoclonal ,General Medicine ,Molecular biology ,Mice, Inbred C57BL ,TLR2 ,030104 developmental biology ,Biochemistry ,chemistry ,Antigens, Surface ,biology.protein ,TLR4 ,Female ,Antibody ,Glycoprotein ,030215 immunology - 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.
- Published
- 2015