Contributions of high mobility group box protein in experimental and clinical acute lung injury
Contributions of high mobility group box protein in experimental and clinical acute lung injury
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DOI：
10.1164/rccm.200402-188oc
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发表时间：
2004-12-15
影响因子：
24.7
通讯作者：
Ishizaka, A
中科院分区：
文献类型：
--
作者：
Ueno, H;Matsuda, T;Ishizaka, A
本研究旨在探讨高迁移率族蛋白B(HMGB)在急性肺损伤(ALI)发病机制中的作用。观察(1)21例败血症ALI患者和15例肺功能正常的患者；(2)小鼠气管内滴注脂多糖(LPS)24小时后的变化。ALI患者血浆和肺上皮细胞衬里液中HMGB1浓度升高，小鼠肺灌洗后HMGB1浓度升高。抗HMGB1抗体可减轻脂多糖诱导的ALI。虽然在对照组的人或小鼠的血浆中没有检测到这种蛋白，但在肺上皮衬里液或支气管肺泡灌洗液中HMGB1的浓度出人意料地高。HMGB1在正常小鼠的终末细支气管周围的上皮细胞中有明显的核表达，而在嘴唇灌输的小鼠肺泡巨噬细胞中有核和胞浆的表达。肺内滴注HMGB2引起的炎症不像HMGB1那样严重。细胞外HMGB1可能在临床和实验性ALI的发病机制中起关键作用。然而，它在正常呼吸道中的表达是值得注意的，这表明它在肺中也起着生理作用。
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 lipopoly-saccharide (LPS). The concentrations of HMGB1 were increased in plasma and lung epithelial lining fluid of patients with ALI and mice instilled with LIPS. 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 LIPS-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.