Mechano-oxidative coupling by mitochondria induces proinflammatory responses in lung venular capillaries.
Mechano-oxidative coupling by mitochondria induces proinflammatory responses in lung venular capillaries.
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线粒体的机械氧化耦合诱导肺小静脉毛细血管的促炎症反应。
DOI：
10.1172/jci17271
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Bhattacharya,Jahar
中科院分区：
文献类型：
--
作者：
Ichimura,Hideo;Parthasarathi,Kaushik;Quadri,Sadiqa;Issekutz,AndrewC;Bhattacharya,Jahar
肺毛细血管压力升高导致内皮细胞（ECs）白细胞粘附受体p -选择素分泌，表明肺内皮细胞对压力诱导的应激产生促炎反应。为了明确潜在的机制，我们在肺毛细血管中应用实时荧光显微镜，跟踪了导致p -选择素胞吐的EC信号序列。压力升高增加了细胞质Ca2+振荡的幅度，从而引发线粒体Ca2+振荡幅度的增加和活性氧（ROS）的产生。对Ca2+振荡和线粒体电子传递阻滞剂的反应表明，ROS的产生依赖于Ca2+，并且来自线粒体。研究揭示了一种新的促炎机制，即抗氧化剂和线粒体抑制剂都能抑制压力诱导的p -选择素的胞吐，表明胞吐是由线粒体ROS驱动的。在这个信号通路中，线粒体将压力诱导的Ca2+振荡耦合到ROS的产生，ROS反过来作为扩散信使激活p -选择素胞外分泌。这些发现暗示了线粒体机制在肺对压力升高的促炎反应中，并确定了线粒体ROS对肺毛细血管内皮细胞中p -选择素胞吐的关键作用。
Elevation of lung capillary pressure causes exocytosis of the leukocyte adhesion receptor P-selectin in endothelial cells (ECs), indicating that lung ECs generate a proinflammatory response to pressure-induced stress. To define underlying mechanisms, we followed the EC signaling sequence leading to P-selectin exocytosis through application of real-time, in situ fluorescence microscopy in lung capillaries. Pressure elevation increased the amplitude of cytosolic Ca2+oscillations that triggered increases in the amplitude of mitochondrial Ca2+oscillations and in reactive oxygen species (ROS) production. Responses to blockers of the Ca2+oscillations and of mitochondrial electron transport indicated that the ROS production was Ca2+dependent and of mitochondrial origin. A new proinflammatory mechanism was revealed in that pressure-induced exocytosis of P-selectin was inhibited by both antioxidants and mitochondrial inhibitors, indicating that the exocytosis was driven by mitochondrial ROS. In this signaling pathway mitochondria coupled pressure-induced Ca2+oscillations to the production of ROS that in turn acted as diffusible messengers to activate P-selectin exocytosis. These findings implicate mitochondrial mechanisms in the lung’s proinflammatory response to pressure elevation and identify mitochondrial ROS as critical to P-selectin exocytosis in lung capillary ECs.
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影响因子：
3.9
作者：
Imrich, A;Kobzik, L
通讯作者：
Kobzik, L
影响因子：
3.9
作者：
ROYALL, JA;ISCHIROPOULOS, H
通讯作者：
ISCHIROPOULOS, H
内毒素诱导的气道炎症中淋巴细胞的剂量依赖性激活
影响因子：
3.1
作者：
R. Larsson;David Rocksén;B. Lilliehöök;Åsa Jonsson;A. Bucht
通讯作者：
A. Bucht
影响因子：
4.4
作者：
N. Chandel;W. Trzyna;D. S. McClintock;P. Schumacker
通讯作者：
N. Chandel;W. Trzyna;D. S. McClintock;P. Schumacker
影响因子：
4.1
作者：
Collins, TJ;Lipp, P;Bootman, MD
通讯作者：
Bootman, MD