Contribution of high-mobility group box-1 to the development of ventilator-induced lung injury

被引:119
作者
Ogawa, Eileen N.
Ishizaka, Akitoshi
Tasaka, Sadatomo
Koh, Hidefumi
Ueno, Hiroshi
Amaya, Fumimasa
Ebina, Masahito
Yamada, Shingo
Funakoshi, Yosuke
Soejima, Junko
Moriyama, Kiyoshi
Kotani, Toru
Hashimoto, Satoru
Morisaki, Hiroshi
Abraham, Edward
Takeda, Junzo
机构
[1] Keio Univ, Sch Med, Dept Med, Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Anesthesiol, Tokyo 1608582, Japan
[3] Tokyo Womens Med Univ, Daini Hosp, Dept Anesthesiol & Intens Care, Tokyo, Japan
[4] Kyoto Prefectural Univ Med, Dept Anesthesiol & Intens Care, Kyoto, Japan
[5] Tohoku Univ, Inst Dev Aging & Canc, Sendai, Miyagi 980, Japan
[6] Shino Test Corp, Cent Inst, Kanagawa, Japan
[7] Ono Pharmaceut Co Ltd, Osaka, Japan
[8] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
关键词
high-mobility group box-1; macrophage; rabbit model; ventilator-induced lung injury;
D O I
10.1164/rccm.200605-699OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Rationale: Proinflammatory cytokines play an important role in ventilator-induced lung injury (VILI). High-mobility group box-1 (HMGB1) is a macrophage-derived proinflammatory cytokine that can cause lung injury. Objectives: This study tested the hypothesis that HMGB1 is released in intact lungs ventilated with large VT. A second objective was to identify the source of HMGB1. A third objective was to examine the effects of blocking HMGB1 on the subsequent development of VILI. Methods: Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained from rabbits mechanically ventilated for 4 h with a small (8 ml/kg) versus a large (30 ml/kg) VT. BALF was also obtained from rabbits with intratracheal instillation of anti-HMGB1 antibody before the initiation of large VT ventilation. Measurements and Main Results: The concentrations of HMGB1 in BALF were fivefold higher in the large than in the small VT group. Immunohistochemistry and immunofluorescence studies revealed expression of HMGB1 in the cytoplasm of macrophages and neutrophils in lungs ventilated with large VT. Blocking HMGB1 improved oxygenation, limited microvascular permeability and neutrophil influx into the alveolar lumen, and decreased concentrations of tumor necrosis factor-alpha in BALF. Conclusions: These observations suggest that HMGB1 could be one of the deteriorating factors in the development of VILI.
引用
收藏
页码:400 / 407
页数:8
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