Contribution of high-mobility group box-1 to the development of ventilator-induced lung injury
Contribution of high-mobility group box-1 to the development of ventilator-induced lung injury
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DOI：
10.1164/rccm.200605-699oc
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发表时间：
2006-08-15
影响因子：
24.7
通讯作者：
Takeda, Junzo
中科院分区：
文献类型：
--
作者：
Ogawa, Eileen N.;Ishizaka, Akitoshi;Takeda, Junzo
原理：促炎细胞因子在呼吸机诱导的肺损伤（VILI）中起重要作用。高迁移率族蛋白1（HMGB 1）是一种巨噬细胞衍生的促炎细胞因子，可导致肺injury.Objectives：本研究测试的假设，即HMGB 1释放在完整的肺通气大VT。第二个目标是确定HMGB 1的来源。第三个目的是研究阻断HMGB 1对VILI.Methods的后续发展的影响：支气管肺泡灌洗液（BALF）和肺组织获得从兔机械通气4小时与一个小（8 ml/kg）与一个大（30 ml/kg）VT。BALF中也获得了大VT ventilation. Measures和主要结果：BALF中HMGB 1的浓度是5倍，比在小VT组开始前，气管内滴注抗HMGB 1抗体。免疫组织化学和免疫荧光研究显示，HMGB 1表达于肺巨噬细胞和中性粒细胞的细胞质中的大VT。阻断HMGB 1可改善肺氧合，限制微血管通透性和中性粒细胞流入肺泡腔，并降低BALF中肿瘤坏死因子-α的浓度。结论：HMGB 1可能是VILI发展过程中的恶化因素之一。
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.