Mendivil Carlos O, Koziel Henry, Brain Joseph D
School of Medicine, Universidad de los Andes, Bogotá, Colombia; Section of Endocrinology, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia; Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2015 Apr 7;10(4):e0123344. doi: 10.1371/journal.pone.0123344. eCollection 2015.
Our current understanding of hormone regulation in lung parenchyma is quite limited. We aimed to quantify a diverse array of biologically relevant protein mediators in alveolar lining fluid (ALF), compared to serum concentrations, and explore factors associated with protein compartmentalization on either side of the air-blood barrier.
Participants were 24 healthy adult non-smoker volunteers without respiratory symptoms or significant medical conditions, with normal lung exams and office spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24 proteins (including enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines) using a highly sensitive multiplex ELISA. Measurements were normalized to ALF concentrations. The ALF:serum concentration ratios were examined in relation to measures of protein size, hydrophobicity, charge, and to participant clinical and spirometric values.
ALF measurements from 24 individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA-II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or serum for any individual. In general, ALF levels were similar or lower in concentration for most proteins compared to serum. However, ghrelin, resistin, insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and resistin correlated with protein net charge and isoelectric point, but not with molecular weight or hydrophobicity.
Biologically relevant enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines can be detected in the ALF of healthy individuals. For the proteins measured, charge may influence trafficking and compartmentalization to the alveolar airspace more than molecular weight or hydrophobicity. These data may have implications for homeostasis and drug delivery to the lung.
我们目前对肺实质中激素调节的了解相当有限。我们旨在定量分析肺泡衬液（ALF）中多种具有生物学相关性的蛋白质介质，并与血清浓度进行比较，同时探究气血屏障两侧与蛋白质分隔相关的因素。
研究对象为24名无呼吸道症状或重大疾病、肺部检查及办公室肺功能检查正常的健康成年非吸烟志愿者。使用高灵敏度多重酶联免疫吸附测定法（ELISA）对无细胞支气管肺泡灌洗液和血清中的24种蛋白质（包括肠道和代谢激素、载脂蛋白、脂肪因子和细胞因子）进行分析。测量值以ALF浓度进行标准化。考察了ALF与血清浓度之比与蛋白质大小、疏水性、电荷以及参与者临床和肺功能测量值之间的关系。
对24名个体的ALF测量发现了19种蛋白质，包括脂联素、脂肪酶、载脂蛋白A-I、载脂蛋白A-II、载脂蛋白B、载脂蛋白C-II、载脂蛋白C-III、载脂蛋白E、C反应蛋白、胃饥饿素、葡萄糖依赖性促胰岛素多肽（GIP）、胰高血糖素样肽-1（GLP-1）、胰高血糖素、胰岛素、瘦素、单核细胞趋化蛋白-1、纤溶酶原激活物抑制剂-1、抵抗素和内脏脂肪素。在任何个体的ALF中均未检测到C肽和丝氨酸蛋白酶抑制剂E1，在任何个体的ALF或血清中均未检测到白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和肿瘤坏死因子-α（TNF-α）。总体而言，与血清相比，大多数蛋白质的ALF水平浓度相似或更低。然而，胃饥饿素、抵抗素、胰岛素、内脏脂肪素和GLP-1的ALF浓度显著高于血清。重要的是，胃饥饿素、内脏脂肪素和抵抗素的ALF与血清浓度之比升高与蛋白质净电荷和等电点相关，但与分子量或疏水性无关。
在健康个体的ALF中可检测到具有生物学相关性的肠道和代谢激素、载脂蛋白、脂肪因子和细胞因子。对于所测量的蛋白质，电荷可能比分子量或疏水性更能影响其向肺泡腔的转运和分隔。这些数据可能对肺内稳态和药物递送具有重要意义。
