Oxygen dose responsiveness of human fetal airway smooth muscle cells
Oxygen dose responsiveness of human fetal airway smooth muscle cells
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DOI：
10.1152/ajplung.00037.2012
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发表时间：
2012-10-01
影响因子：
4.9
通讯作者：
Pabelick, Christina M.
中科院分区：
文献类型：
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作者：
Hartman, William R.;Smelter, Dan F.;Pabelick, Christina M.
Hartman WR、Smelter DF、Sathish V、Karass M、Kim S、Aravamudan B、Thompson MA、Amrani Y、Pandya HC、Martin RJ、Prakash YS、Pabelick CM。人胎儿气道平滑肌细胞的氧剂量反应。 Am J Physiol Lung Cell Mol Physiol 303: L711-L719, 2012。首次发表于 2012 年 8 月 24 日； doi:10.1152/ajplung.00037.2012.-维持血氧饱和度需要对早产儿进行补充供氧，但高氧血症使幸存者容易患哮喘等呼吸系统疾病。尽管许多研究都集中在支气管肺发育不良情况下氧气对肺泡的影响，但氧气影响与哮喘相关的气道结构或功能的机制仍在研究中。我们使用来自 18-20 岁孕后肺（小管阶段）的分离人胎儿气道平滑肌 (fASM) 细胞来检查氧对细胞内 Ca2+ ([Ca2+](i)) 和细胞增殖的影响。 fASM 细胞表达大量平滑肌肌动蛋白和肌球蛋白以及多种 Ca2+ 调节蛋白，但不表达成纤维细胞或上皮标记物，其特征在质量上与成人 ASM 相当。荧光 Ca2+ 成像显示对 1 muM 乙酰胆碱 (ACh) 和 10 muM 组胺（尽管比成人 ASM 更小且更慢）有强烈的 [Ca2+](i) 反应，对零细胞外 Ca2+ 部分敏感。与成人相比，fASM 显示出更大的基线增殖。基于此验证，我们评估了 fASM 对 10% 缺氧到 90% 高氧的反应，发现 60% 时增殖增强，伴随着增殖与凋亡标记物适当变化的效应，以及 > 60% 氧时线粒体裂变增强。 [Ca2+](i) 对 ACh 的反应在 60% 的氧气下增强。这些结果表明，高氧对发育中的 ASM 的结构和功能具有剂量依赖性影响，这可能对儿童气道疾病产生影响。因此，在评估早产儿补充氧气的风险时，应额外考虑对 ASM 的有害影响。
Hartman WR, Smelter DF, Sathish V, Karass M, Kim S, Aravamudan B, Thompson MA, Amrani Y, Pandya HC, Martin RJ, Prakash YS, Pabelick CM. Oxygen dose responsiveness of human fetal airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 303: L711-L719, 2012. First published August 24, 2012; doi:10.1152/ajplung.00037.2012.-Maintenance of blood oxygen saturation dictates supplemental oxygen administration to premature infants, but hyperoxia predisposes survivors to respiratory diseases such as asthma. Although much research has focused on oxygen effects on alveoli in the setting of bronchopulmonary dysplasia, the mechanisms by which oxygen affects airway structure or function relevant to asthma are still under investigation. We used isolated human fetal airway smooth muscle (fASM) cells from 18-20 post-conceptual age lungs (canalicular stage) to examine oxygen effects on intracellular Ca2+ ([Ca2+](i)) and cellular proliferation. fASM cells expressed substantial smooth muscle actin and myosin and several Ca2+ regulatory proteins but not fibroblast or epithelial markers, profiles qualitatively comparable to adult human ASM. Fluorescence Ca2+ imaging showed robust [Ca2+](i) responses to 1 mu M acetylcholine (ACh) and 10 mu M histamine (albeit smaller and slower than adult ASM), partly sensitive to zero extracellular Ca2+. Compared with adult, fASM showed greater baseline proliferation. Based on this validation, we assessed fASM responses to 10% hypoxia through 90% hyperoxia and found enhanced proliferation at 60%, effects accompanied by appropriate changes in proliferative vs. apoptotic markers and enhanced mitochondrial fission at >60% oxygen. [Ca2+](i) responses to ACh were enhanced for 60% oxygen. These results suggest that hyperoxia has dose-dependent effects on structure and function of developing ASM, which could have consequences for airway diseases of childhood. Thus detrimental effects on ASM should be an additional consideration in assessing risks of supplemental oxygen in prematurity.