TRPV4 channels augment macrophage activation and ventilator-induced lung injury
TRPV4 channels augment macrophage activation and ventilator-induced lung injury
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DOI：
10.1152/ajplung.00315.2009
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发表时间：
2010-09-01
影响因子：
4.9
通讯作者：
Parker, James C.
中科院分区：
文献类型：
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作者：
Hamanaka, Kazutoshi;Jian, Ming-Yuan;Parker, James C.
Hamanaka K、Jian MY、Townsley MI、King JA、Liedtke W、Weber DS、Eyal FG、Clapp MM、Parker JC。 TRPV4 通道增强巨噬细胞激活和呼吸机引起的肺损伤。 Am J Physiol Lung Cell Mol Physiol 299：L353-L362，2010。首次发表于 2010 年 6 月 18 日； doi:10.1152/ajplung.00315.2009.-我们之前已经发现瞬时受体电位香草酸 4 (TRPV4) 通道和肺泡巨噬细胞在响应高峰值充气压力 (PIP) 通气时启动通透性增加。从 TRPV4(-/-) 和 TRPV4(-/-) 小鼠中收获肺泡巨噬细胞，并将其注入相反基因型小鼠的肺部。在连续 30 分钟的 9、25 和 35 cmH(2)O PIP 通气后，在离体灌注肺中测量的过滤系数 (K-f) 在 TRPV4(-/-) 小鼠的肺中没有显着增加，但在 TRPV4(-/-) 肺、灌输 TRPV4(-/-) 的 TRPV4(-/-) 肺中增加 > 2.2 倍 巨噬细胞和 TRPV4(-/-) 肺在用 35 cmH(2)O PIP 通气后注入 TRPV4(-/-) 巨噬细胞。用 4-α-佛波醇二癸酸酯 (4α PDD) 激活 TRPV4 显着增加 TRPV4(-/-) 巨噬细胞内钙、超氧化物和一氧化氮的产生，但 TRPV4(-/-) 巨噬细胞则不然。 4 α PDD 后，与 TRPV4(-/-) 巨噬细胞相比，TRPV4(-/-) 巨噬细胞的横截面积增加了近 3 倍。肺组织的硝基酪氨酸免疫组织化学染色显示，与低 PIP 通气 TRPV4(-/-) 或高 PIP 通气 TRPV4(-/-) 肺相比，高 PIP 通气 TRPV4(-/-) 肺中硝基酪氨酸的量增加。因此TRPV4(-/-)巨噬细胞恢复了TRPV4(-/-)肺对机械损伤的敏感性。 TRPV4激动剂增加收获的TRPV4(-/-)巨噬细胞中的细胞内钙、活性氧和氮物种，但不增加TRPV4(-/-)巨噬细胞。 Kf 的增加与组织硝基酪氨酸（过氧亚硝酸盐产生的标志物）相关。
Hamanaka K, Jian MY, Townsley MI, King JA, Liedtke W, Weber DS, Eyal FG, Clapp MM, Parker JC. TRPV4 channels augment macrophage activation and ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 299: L353-L362, 2010. First published June 18, 2010; doi:10.1152/ajplung.00315.2009.-We have previously implicated transient receptor potential vanilloid 4 (TRPV4) channels and alveolar macrophages in initiating the permeability increase in response to high peak inflation pressure (PIP) ventilation. Alveolar macrophages were harvested from TRPV4(-/-) and TRPV4(-/-) mice and instilled in the lungs of mice of the opposite genotype. Filtration coefficients (K-f) measured in isolated perfused lungs after ventilation with successive 30-min periods of 9, 25, and 35 cmH(2)O PIP did not significantly increase in lungs from TRPV4(-/-) mice but increased >2.2-fold in TRPV4(-/-) lungs, TRPV4(-/-) lungs instilled with TRPV4(-/-) macrophages, and TRPV4(-/-) lungs instilled with TRPV4(-/-) macrophages after ventilation with 35 cmH(2)O PIP. Activation of TRPV4 with 4-alpha-phorbol didecanoate (4 alpha PDD) significantly increased intracellular calcium, superoxide, and nitric oxide production in TRPV4(-/-) macrophages but not TRPV4(-/-) macrophages. Cross-sectional areas increased nearly 3-fold in TRPV4(-/-) macrophages compared with TRPV4(-/-) macrophages after 4 alpha PDD. Immunohistochemistry staining of lung tissue for nitrotyrosine revealed increased amounts in high PIP ventilated TRPV4(-/-) lungs compared with low PIP ventilated TRPV4(-/-) or high PIP ventilated TRPV4(-/-) lungs. Thus TRPV4(-/-) macrophages restored susceptibility of TRPV4(-/-) lungs to mechanical injury. A TRPV4 agonist increased intracellular calcium and reactive oxygen and nitrogen species in harvested TRPV4(-/-) macrophages but not TRPV4(-/-) macrophages. Kf increases correlated with tissue nitrotyrosine, a marker of peroxynitrite production.