Extracellular heat shock protein 72 is a marker of the stress protein response in acute lung injury
Extracellular heat shock protein 72 is a marker of the stress protein response in acute lung injury
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DOI：
10.1152/ajplung.00405.2005
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发表时间：
2006-09-01
影响因子：
4.9
通讯作者：
Pittet, Jean-Francois
中科院分区：
文献类型：
--
作者：
Ganter, Michael T.;Ware, Lorraine B.;Pittet, Jean-Francois
热休克蛋白72（heat shock protein 72，Hsp 72）存在于细胞外空间（eHsp 72）中，具有较强的免疫调节作用。然而，eHsp 72是否存在于远端的空气空间，以及eHsp 72是否可以调节肺泡水肿的消除尚不清楚。第一个目的是确定Hsp 72是否在空气空间内释放，以及肺水肿液中的Hsp 72水平是否与ALI/ARDS患者肺泡上皮细胞清除肺泡水肿液的能力相关。以流体静力性水肿患者作为对照。第二个目的是确定应激蛋白应答（SPR）的激活是否导致体内和体外Hsp 72释放到细胞外空间，并确定SPR激活和/或eHsp 72本身是否会阻止IL-1 β介导的对跨肺泡II型细胞的载体液体转运的抑制。我们发现，eHsp 72存在于血浆和肺水肿液中的ALI患者和eHsp 72是显着较高的肺水肿液中保存肺泡上皮液体清除的患者。此外，SPR在小鼠体内和体外肺内皮细胞，上皮细胞和巨噬细胞中的激活引起Hsp 72的细胞内表达和细胞外释放。最后，SPR激活，而不是eHsp 72本身，阻止了暴露于IL-1 β诱导的肺泡上皮细胞离子转运的减少。因此，SPR可以保护肺泡上皮细胞免受氧化应激相关的实验性ALI，和eHsp 72可以作为SPR激活的ALI患者的远端空气空间的标志物。
Previous studies have shown that heat shock protein 72 (Hsp72) is found in the extracellular space (eHsp72) and that eHsp72 has potent immunomodulatory effects. However, whether eHsp72 is present in the distal air spaces and whether eHsp72 could modulate removal of alveolar edema is unknown. The first objective was to determine whether Hsp72 is released within air spaces and whether Hsp72 levels in pulmonary edema fluid would correlate with the capacity of the alveolar epithelium to remove alveolar edema fluid in patients with ALI/ARDS. Patients with hydrostatic edema served as controls. The second objective was to determine whether activation of the stress protein response (SPR) caused the release of Hsp72 into the extracellular space in vivo and in vitro and to determine whether SPR activation and/or eHsp72 itself would prevent the IL-1 beta-mediated inhibition of the vectorial fluid transport across alveolar type II cells. We found that eHsp72 was present in plasma and pulmonary edema fluid of ALI patients and that eHsp72 was significantly higher in pulmonary edema fluid from patients with preserved alveolar epithelial fluid clearance. Furthermore, SPR activation in vivo in mice and in vitro in lung endothelial, epithelial, and macrophage cells caused intracellular expression and extracellular release of Hsp72. Finally, SPR activation, but not eHsp72 itself, prevented the decrease in alveolar epithelial ion transport induced by exposure to IL-1 beta. Thus SPR may protect the alveolar epithelium against oxidative stress associated with experimental ALI, and eHsp72 may serve as a marker of SPR activation in the distal air spaces of patients with ALI.