Ma Daniel C, Yoon Alexander J, Faull Kym F, Desharnais Robert, Zemanick Edith T, Porter Edith
Department of Biological Sciences, California State University Los Angeles, Los Angeles, California, United States of America.
Pasarow Mass Spectrometry Laboratory, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2015 Apr 28;10(4):e0125326. doi: 10.1371/journal.pone.0125326. eCollection 2015.
Host-derived lipids including cholesteryl esters (CEs) such as cholesteryl linoleate have emerged as important antibacterial effectors of innate immunity in the airways and cholesteryl linoleate has been found elevated in the context of inflammation. Cystic fibrosis (CF) patients suffer from chronic infection and severe inflammation in the airways. Here, we identified and quantified CEs in bronchoalveolar lavage fluid (BALF) from CF patients and non-CF disease controls, and tested whether CE concentrations are linked to the disease.
CEs in BALF from 6 pediatric subjects with CF and 7 pediatric subjects with non-CF chronic lung disease were quantified by mass spectral analysis using liquid chromatography coupled with tandem mass spectrometry and multiple reaction monitoring. BALFs were also examined for total lipid, total protein, albumin, and, as a marker for inflammation, human neutrophil peptide (HNP) 1-3 concentrations. Statistical analysis was conducted after log 10 transformation of the data.
Total lipid/protein ratio was reduced in CF BALF (p = 0.018) but the concentrations of CEs, including cholesteryl linoleate, were elevated in the total lipid fraction in CF BALF compared to non-CF disease controls (p < 0.050). In addition, the concentrations of CEs and HNP1-3 correlated with one another (p < 0.050).
The data suggests that the lipid composition of BALF is altered in CF with less total lipid relative to protein but with increased CE concentrations in the lipid fraction, likely contributed by inflammation. Future longitudinal studies may reveal the suitability of CEs as a novel biomarker for CF disease activity which may provide new information on the lipid mediated pathophysiology of the disease.
包括胆固醇酯(CEs)如亚油酸胆固醇酯在内的宿主衍生脂质已成为气道先天免疫的重要抗菌效应物,并且已发现在炎症情况下亚油酸胆固醇酯水平升高。囊性纤维化(CF)患者患有气道慢性感染和严重炎症。在此,我们鉴定并定量了CF患者和非CF疾病对照的支气管肺泡灌洗液(BALF)中的CEs,并测试了CE浓度是否与该疾病相关。
使用液相色谱-串联质谱和多反应监测,通过质谱分析对6名患有CF的儿科受试者和7名患有非CF慢性肺病的儿科受试者的BALF中的CEs进行定量。还检测了BALF中的总脂质、总蛋白、白蛋白,以及作为炎症标志物的人中性粒细胞肽(HNP)1-3浓度。数据经log10转换后进行统计分析。
CF患者的BALF中总脂质/蛋白比值降低(p = 0.018),但与非CF疾病对照相比,CF患者的BALF中总脂质部分中包括亚油酸胆固醇酯在内的CEs浓度升高(p < 0.050)。此外,CEs浓度与HNP1-3浓度相互相关(p < 0.050)。
数据表明,CF患者BALF的脂质组成发生改变,相对于蛋白质而言总脂质减少,但脂质部分中的CEs浓度增加,这可能是由炎症导致的。未来的纵向研究可能会揭示CEs作为CF疾病活动新生物标志物的适用性,这可能会为该疾病的脂质介导病理生理学提供新信息。