Pulmonary surfactant function is abolished by an elevated proportion of cholesterol
Pulmonary surfactant function is abolished by an elevated proportion of cholesterol
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DOI：
10.1016/j.bbalip.2005.09.002
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发表时间：
2005-10-15
影响因子：
4.8
通讯作者：
Amrein, M
中科院分区：
文献类型：
--
作者：
Gunasekara, L;Sch端rch, S;Amrein, M
肺表面活性剂的分子膜强烈降低肺上皮-空气界面的表面张力。人肺表面活性物质含有5- 10质量%的胆固醇，以及其他脂质和表面活性物质特异性蛋白质。从急性肺损伤（ALI）中恢复的表面活性剂中发现胆固醇比例升高。胆固醇在肺表面活性物质中的功能作用仍存在争议。胆固醇被排除在大多数肺表面活性物质替代制剂之外，临床上用于治疗表面活性物质缺乏症。这是因为胆固醇在体外已经显示出即使在生理水平也会损害表面活性剂的表面活性。在目前的研究中，胆固醇的功能作用已重新评估使用改进的方法，在体外评估表面活性，捕获气泡表面活性仪（CBS）。将胆固醇添加到临床使用的治疗表面活性剂之一BLES（牛脂质提取物表面活性剂）中，并评价表面活性，包括物质对空气-水界面的吸附速率、其产生接近于零的表面张力的能力以及获得低表面张力所需的面积压缩。对于不含胆固醇、含5或10%胆固醇的BLES样品，在最小表面张力方面没有发现表面活性的差异。因此，我们的研究结果表明，先前描述的生理量的胆固醇的有害影响与实验方法有关。然而，在20%时，胆固醇有效地消除了表面活性剂功能，并且没有获得低于15 mN/m的表面张力。因此，胆固醇对表面活性的抑制可能部分或完全解释ALI病例中肺功能受损的原因。我们讨论了一种分子机制，可以解释为什么胆固醇不能防止低表面活性剂膜的表面张力在生理水平，但废除表面活性剂功能在较高的水平。(c)2005 Elsevier B. V.保留所有权利。
A molecular film of pulmonary surfactant strongly reduces the surface tension of the lung epithelium-air interface. Human pulmonary surfactant contains 5-10% cholesterol by mass, among other lipids and surfactant specific proteins. An elevated proportion of cholesterol is found in surfactant, recovered from acutely injured lungs (ALI). The functional role of cholesterol in pulmonary surfactant has remained controversial. Cholesterol is excluded from most pulmonary surfactant replacement formulations, used clinically to treat conditions of surfactant deficiency. This is because cholesterol has been shown in vitro to impair the surface activity of surfactant even at a physiological level. In the current study, the functional role of cholesterol has been re-evaluated using an improved method of evaluating surface activity in vitro, the captive bubble surfactometer (CBS). Cholesterol was added to one of the clinically used therapeutic surfactants, BLES, a bovine lipid extract surfactant, and the surface activity evaluated, including the adsorption rate of the substance to the air-water interface, its ability to produce a surface tension close to zero and the area compression needed to obtain that low surface tension. No differences in the surface activity were found for BLES samples containing either none, 5 or 10% cholesterol by mass with respect to the minimal surface tension. Our findings therefore suggest that the earlier-described deleterious effects of physiological amounts of cholesterol are related to the experimental methodology. However, at 20%, cholesterol effectively abolished surfactant function and a surface tension below 15 mN/m was not obtained. Inhibition of surface activity by cholesterol may therefore partially or fully explain the impaired lung function in the case of ALI. We discuss a molecular mechanism that could explain why cholesterol does not prevent low surface tension of surfactant films at physiological levels but abolishes surfactant function at higher levels. (c) 2005 Elsevier B.V. All rights reserved.