This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200402-188OCv1 170/12/1310    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ueno, H. Articles by Ishizaka, A. Search for Related Content PubMed PubMed Citation Articles by Ueno, H. Articles by Ishizaka, A.

Contributions of High Mobility Group Box Protein in Experimental and Clinical Acute Lung Injury

Department of Anesthesiology and Intensive Care; Department of Anatomy, Kyoto Prefectural University of Medicine, Kyoto; Intensive Care Unit, Saiseikai Suita Hospital, Osaka; Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima; and Department of Medicine, Keio University, Tokyo, Japan

Correspondence and requests for reprints should be addressed to Satoru Hashimoto, M.D., Department of Intensive Care and Anesthesiology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan, 602–8566. E-mail: satoru{at}koto.kpu-m.ac.jp

This study was performed to examine the putative role of high mobility group box (HMGB) protein in the pathogenesis of acute lung injury (ALI). Observations were made (1) in 21 patients who were septic with ALI and 15 patients with normal lung function and (2) in a mouse model 24 hours after intratracheal instillation of lipopolysaccharide (LPS). The concentrations of HMGB1 were increased in plasma and lung epithelial lining fluid of patients with ALI and mice instilled with LPS. LPS-induced ALI was mitigated by anti-HMGB1 antibody. Although this protein was not detected in the plasma of control humans or mice, the concentrations of HMGB1 in lung epithelial lining fluid or in bronchoalveolar lavage fluid were unexpectedly high. The nuclear expression of HMGB1 was apparent in epithelial cells surrounding terminal bronchioles in normal mice, whereas its nuclear and cytoplasmic expression was observed in alveolar macrophages in LPS-instilled mice. Lung instillation of HMGB2 did not cause as much inflammation as HMGB1. Extracellular HMGB1 may play a key role in the pathogenesis of clinical and experimental ALI. However, its expression in normal airways is noteworthy and suggests that it also plays a physiologic role in the lung.

Key Words: acute respiratory distress syndrome • endotoxin • high mobility group B-1 protein • high mobility group B-2 protein • lipopolysaccharide

This article has been cited by other articles:

				D. Tang, R. Kang, W. Xiao, H. Zhang, M. T. Lotze, H. Wang, and X. Xiao Quercetin Prevents LPS-Induced High-Mobility Group Box 1 Release and Proinflammatory Function Am. J. Respir. Cell Mol. Biol., December 1, 2009; 41(6): 651 - 660. [Abstract] [Full Text] [PDF]

				E. Kamau, R. Takhampunya, T. Li, E. Kelly, K. K. Peachman, J. A. Lynch, P. Sun, and D. R. Palmer Dengue virus infection promotes translocation of high mobility group box 1 protein from the nucleus to the cytosol in dendritic cells, upregulates cytokine production and modulates virus replication J. Gen. Virol., August 1, 2009; 90(8): 1827 - 1835. [Abstract] [Full Text] [PDF]

				T. Kohno, T. Anzai, K. Naito, T. Miyasho, M. Okamoto, H. Yokota, S. Yamada, Y. Maekawa, T. Takahashi, T. Yoshikawa, et al. Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling Cardiovasc Res, February 15, 2009; 81(3): 565 - 573. [Abstract] [Full Text] [PDF]

				A. Tajima, M. Kohno, M. Watanabe, Y. Izumi, S. Tasaka, I. Maruyama, T. Miyasho, and K. Kobayashi Occult injury in the residual lung after pneumonectomy in mice Interactive CardioVascular and Thoracic Surgery, December 1, 2008; 7(6): 1114 - 1120. [Abstract] [Full Text] [PDF]

				S. Hashimoto, F. Amaya, H. Matsuyama, H. Ueno, S. Kikuchi, M. Tanaka, Y. Watanabe, M. Ebina, A. Ishizaka, S. Tsukita, et al. Dysregulation of lung injury and repair in moesin-deficient mice treated with intratracheal bleomycin Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L566 - L574. [Abstract] [Full Text] [PDF]

				I. A. J. Giebelen, M. Leendertse, M. C. Dessing, J. C. M. Meijers, M. Levi, C. Draing, S. von Aulock, and T. van der Poll Endogenous {beta}-Adrenergic Receptors Inhibit Lipopolysaccharide-Induced Pulmonary Cytokine Release and Coagulation Am. J. Respir. Cell Mol. Biol., September 1, 2008; 39(3): 373 - 379. [Abstract] [Full Text] [PDF]

				H. Zhang, S. Tasaka, Y. Shiraishi, K. Fukunaga, W. Yamada, H. Seki, Y. Ogawa, K. Miyamoto, Y. Nakano, N. Hasegawa, et al. Role of Soluble Receptor for Advanced Glycation End Products on Endotoxin-induced Lung Injury Am. J. Respir. Crit. Care Med., August 15, 2008; 178(4): 356 - 362. [Abstract] [Full Text] [PDF]

				K. Liu, S. Mori, H. K. Takahashi, Y. Tomono, H. Wake, T. Kanke, Y. Sato, N. Hiraga, N. Adachi, T. Yoshino, et al. Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats FASEB J, December 1, 2007; 21(14): 3904 - 3916. [Abstract] [Full Text] [PDF]

				M. van der Toorn, D.-J. Slebos, H. G. de Bruin, H. G. Leuvenink, S. J. L. Bakker, R. O. B. Gans, G. H. Koeter, A. J. M. van Oosterhout, and H. F. Kauffman Cigarette smoke-induced blockade of the mitochondrial respiratory chain switches lung epithelial cell apoptosis into necrosis Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1211 - L1218. [Abstract] [Full Text] [PDF]

				W. Li, J. Li, M. Ashok, R. Wu, D. Chen, L. Yang, H. Yang, K. J. Tracey, P. Wang, A. E. Sama, et al. A Cardiovascular Drug Rescues Mice from Lethal Sepsis by Selectively Attenuating a Late-Acting Proinflammatory Mediator, High Mobility Group Box 1 J. Immunol., March 15, 2007; 178(6): 3856 - 3864. [Abstract] [Full Text] [PDF]

				V. Urbonaviciute, B. G. Furnrohr, C. Weber, M. Haslbeck, S. Wilhelm, M. Herrmann, and R. E. Voll Factors masking HMGB1 in human serum and plasma J. Leukoc. Biol., January 1, 2007; 81(1): 67 - 74. [Abstract] [Full Text] [PDF]

				T. Weng, Z. Chen, N. Jin, L. Gao, and L. Liu Gene expression profiling identifies regulatory pathways involved in the late stage of rat fetal lung development Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L1027 - L1037. [Abstract] [Full Text] [PDF]

				E. N. Ogawa, A. Ishizaka, S. Tasaka, H. Koh, H. Ueno, F. Amaya, M. Ebina, S. Yamada, Y. Funakoshi, J. Soejima, et al. Contribution of High-Mobility Group Box-1 to the Development of Ventilator-induced Lung Injury Am. J. Respir. Crit. Care Med., August 15, 2006; 174(4): 400 - 407. [Abstract] [Full Text] [PDF]

				A. Jaulmes, S. Thierry, B. Janvier, M. Raymondjean, and V. Marechal Activation of sPLA2-IIA and PGE2 production by high mobility group protein B1 in vascular smooth muscle cells sensitized by IL-1{beta} FASEB J, August 1, 2006; 20(10): 1727 - 1729. [Abstract] [Full Text] [PDF]

				H. Wang, W. Li, J. Li, B. Rendon-Mitchell, M. Ochani, M. Ashok, L. Yang, H. Yang, K. J. Tracey, P. Wang, et al. The Aqueous Extract of a Popular Herbal Nutrient Supplement, Angelica sinensis, Protects Mice against Lethal Endotoxemia and Sepsis J. Nutr., February 1, 2006; 136(2): 360 - 365. [Abstract] [Full Text] [PDF]

				H. Yang, H. Wang, C. J. Czura, and K. J. Tracey The cytokine activity of HMGB1 J. Leukoc. Biol., July 1, 2005; 78(1): 1 - 8. [Abstract] [Full Text] [PDF]

				D. Angus, A. Ishizaka, M. Matthay, F. Lemaire, W. MacNee, and E. Abraham Critical Care in AJRCCM 2004 Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 537 - 544. [Full Text] [PDF]