Elevated peptides in lung lavage fluid associated with bronchiolitis obliterans syndrome.

Elevated peptides in lung lavage fluid associated with bronchiolitis obliterans syndrome.
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DOI:
10.1371/journal.pone.0084471
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Wendt CH
Wendt CH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Stone MD;Harvey SB;Nelsestuen GL;Reilly C;Hertz MI;Wendt CH

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这项发现级研究的目的是使用质谱法来鉴定肺移植受者的支气管肺泡灌洗液中与闭塞性细支气管炎综合征相关的低质量化合物。使用 ESI-TOF 质谱法评估肺移植受者的支气管肺泡灌洗液样本中的小分子,并将其与闭塞性细支气管炎综合征的发生相关联。通过 MS/MS 分析分别鉴定与闭塞性细支气管炎综合征患者和对照样本相关的肽。患有闭塞性细支气管炎综合征的个体的平均支气管肺泡灌洗液 MS 谱图与对照组相比有很大差异。对照组表现出密切的样本间相关性(R = 0.97+/-0.02,平均+/-SD),而闭塞性细支气管炎综合征则表现出更大的异质性(R = 0.86+/-0.09,平均+/-SD)。我们确定了 89 个可预测发生 1 级 BOS 的特征,以及 66 个可预测发生 2 级或更高级别 BOS 的特征。合并来自 MS 分析的级分并评估肽含量。与对照组相比,闭塞性细支气管炎综合征中的肽含量增加了近 10 倍。 C 末端残基表明,与闭塞性细支气管炎综合征患者的弹性蛋白酶型酶相比,对照组具有胰蛋白酶样特异性。质谱检测发现,闭塞性细支气管炎综合征患者的支气管肺泡灌洗液中低质量成分有所增加。其中许多特征是可能由中性粒细胞弹性蛋白酶活性升高引起的肽。
The objective of this discovery-level investigation was to use mass spectrometry to identify low mass compounds in bronchoalveolar lavage fluid from lung transplant recipients that associate with bronchiolitis obliterans syndrome. Bronchoalveolar lavage fluid samples from lung transplant recipients were evaluated for small molecules using ESI-TOF mass spectrometry and correlated to the development of bronchiolitis obliterans syndrome. Peptides associated with samples from persons with bronchiolitis obliterans syndrome and controls were identified separately by MS/MS analysis. The average bronchoalveolar lavage fluid MS spectrum profile of individuals that developed bronchiolitis obliterans syndrome differed greatly compared to controls. Controls demonstrated close inter-sample correlation (R = 0.97+/−0.02, average+/−SD) while bronchiolitis obliterans syndrome showed greater heterogeneity (R = 0.86+/−0.09, average+/−SD). We identified 89 features that were predictive of developing BOS grade 1 and 66 features predictive of developing BOS grade 2 or higher. Fractions from MS analysis were pooled and evaluated for peptide content. Nearly 10-fold more peptides were found in bronchiolitis obliterans syndrome relative to controls. C-terminal residues suggested trypsin-like specificity among controls compared to elastase-type enzymes among those with bronchiolitis obliterans syndrome. Bronchoalveolar lavage fluid from individuals with bronchiolitis obliterans syndrome has an increase in low mass components detected by mass spectrometry. Many of these features were peptides that likely result from elevated neutrophil elastase activity.
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发表时间: 2002-01-01
影响因子: 5.8
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