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High-Mobility Group Box 1: Missing Link Between Thrombosis and Inflammation?

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Recent Advances in Thrombosis and Hemostasis 2008

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Abstract

High-mobility group box 1 protein (HMGB1) is an abundant nuclear protein with a dual function. Inside the cell, HMGB1 binds to DNA and modulates a variety of intranuclear processes, including transcription. Outside the cell, HMGB1 acts as a signal of tissue damage and can promote inflammation, immune responses, and tissue regeneration. During sepsis and/or disseminated intravascular coagulation, however, massive accumulation of HMGB1 in the systemic circulation can cause multiple organ failure and a subsequent lethal outcome. HMGB1 in the systemic circulation is recognized as a lethal mediator of sepsis and a promising therapeutic target for sepsis. Thrombomodulin (TM), a natural anticoagulant glycoprotein expressed on the surface of endothelial cells, plays an important role in sequestering HMGB1. TM may prevent HMGB1 from reaching remote organs, thereby restricting the range of HMGB1 action to the site of injury. In this chapter, we review recent progress made in defining the physiological and pathological roles of HMGB1 and therapeutic strategies aimed at blocking HMGB1.

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Authors and Affiliations

  1. Laboratory and Vascular Medicine, Cardiovascular and Respiratory Disorders, Advanced Therapeutics Course, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Takashi Ito, Ko-ichi Kawahara, Teruto Hashiguchi & Ikuro Maruyama

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  1. Takashi Ito
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  2. Ko-ichi Kawahara
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  3. Teruto Hashiguchi
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  4. Ikuro Maruyama
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Editors and Affiliations

  1. Department of Pathology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kenzo Tanaka M.D., Ph.D. (Professor Emeritus) (Professor Emeritus)

  2. Department of Biochemistry, University of Washington, J317 Health Science Center, Box 357350, Seattle, WA, 98195, USA

    Earl W. Davie Ph.D. (Professor) (Professor)

  3. School of Medicine, Internal Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Yasuo Ikeda M.D., Ph.D. (Professor) (Professor)

  4. Department of Biology, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan

    Sadaaki Iwanaga Ph.D. (Professor Emeritus) (Professor Emeritus)

  5. Department of Medicine, Nagoya University, 26 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Hidehiko Saito M.D., Ph.D. (Professor Emeritus) (Professor Emeritus)

  6. Pathophysiological and Experimental Division, Department of Pathology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Katsuo Sueishi M.D., Ph.D. (Professor) (Professor)

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Ito, T., Kawahara, Ki., Hashiguchi, T., Maruyama, I. (2008). High-Mobility Group Box 1: Missing Link Between Thrombosis and Inflammation?. In: Tanaka, K., Davie, E.W., Ikeda, Y., Iwanaga, S., Saito, H., Sueishi, K. (eds) Recent Advances in Thrombosis and Hemostasis 2008. Springer, Tokyo. https://doi.org/10.1007/978-4-431-78847-8_11

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  • DOI: https://doi.org/10.1007/978-4-431-78847-8_11

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