Inflammatory responses increase secretion of MD-1 protein

Richard Thomas Jennings, Erdenezaya Odkhuu, Akina Nakashima, Naoko Morita, Toshihiko Kobayashi, Ikuko Yamai, Miyako Tanaka, Takayoshi Suganami, Sanae Haga, Michitaka Ozaki, Yasuharu Watanabe, Yoshinori Nagai, Kiyoshi Takatsu, Takane Kikuchi-Ueda, Isao Ichimonji, Yoshihiro Ogawa, Hidekazu Takagi, Tatsuya Yamazaki, Kensuke Miyake, Sachiko Akashi-Takamura

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)503-512
Number of pages10
JournalInternational Immunology
Volume28
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

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Toll-Like Receptor 4
Ligands
B-Lymphocytes
Serum
Proteins
Reperfusion Injury
Ligation
Phospholipids
Glycoproteins
Biomarkers
Macrophages
Monoclonal Antibodies
Urine
Diet
Polymerase Chain Reaction
Injections
Infection

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Jennings, R. T., Odkhuu, E., Nakashima, A., Morita, N., Kobayashi, T., Yamai, I., ... Akashi-Takamura, S. (2016). Inflammatory responses increase secretion of MD-1 protein. International Immunology, 28(10), 503-512. https://doi.org/10.1093/intimm/dxw031

Inflammatory responses increase secretion of MD-1 protein. / Jennings, Richard Thomas; Odkhuu, Erdenezaya; Nakashima, Akina; Morita, Naoko; Kobayashi, Toshihiko; Yamai, Ikuko; Tanaka, Miyako; Suganami, Takayoshi; Haga, Sanae; Ozaki, Michitaka; Watanabe, Yasuharu; Nagai, Yoshinori; Takatsu, Kiyoshi; Kikuchi-Ueda, Takane; Ichimonji, Isao; Ogawa, Yoshihiro; Takagi, Hidekazu; Yamazaki, Tatsuya; Miyake, Kensuke; Akashi-Takamura, Sachiko.

In: International Immunology, Vol. 28, No. 10, 01.10.2016, p. 503-512.

Research output: Contribution to journalArticle

Jennings, RT, Odkhuu, E, Nakashima, A, Morita, N, Kobayashi, T, Yamai, I, Tanaka, M, Suganami, T, Haga, S, Ozaki, M, Watanabe, Y, Nagai, Y, Takatsu, K, Kikuchi-Ueda, T, Ichimonji, I, Ogawa, Y, Takagi, H, Yamazaki, T, Miyake, K & Akashi-Takamura, S 2016, 'Inflammatory responses increase secretion of MD-1 protein', International Immunology, vol. 28, no. 10, pp. 503-512. https://doi.org/10.1093/intimm/dxw031
Jennings RT, Odkhuu E, Nakashima A, Morita N, Kobayashi T, Yamai I et al. Inflammatory responses increase secretion of MD-1 protein. International Immunology. 2016 Oct 1;28(10):503-512. https://doi.org/10.1093/intimm/dxw031
Jennings, Richard Thomas ; Odkhuu, Erdenezaya ; Nakashima, Akina ; Morita, Naoko ; Kobayashi, Toshihiko ; Yamai, Ikuko ; Tanaka, Miyako ; Suganami, Takayoshi ; Haga, Sanae ; Ozaki, Michitaka ; Watanabe, Yasuharu ; Nagai, Yoshinori ; Takatsu, Kiyoshi ; Kikuchi-Ueda, Takane ; Ichimonji, Isao ; Ogawa, Yoshihiro ; Takagi, Hidekazu ; Yamazaki, Tatsuya ; Miyake, Kensuke ; Akashi-Takamura, Sachiko. / Inflammatory responses increase secretion of MD-1 protein. In: International Immunology. 2016 ; Vol. 28, No. 10. pp. 503-512.
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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.",
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AU - Yamai, Ikuko

AU - Tanaka, Miyako

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AU - Haga, Sanae

AU - Ozaki, Michitaka

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AU - Kikuchi-Ueda, Takane

AU - Ichimonji, Isao

AU - Ogawa, Yoshihiro

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AU - Akashi-Takamura, Sachiko

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