特发性肺纤维化患者血管和肺部中 SP-A 和 SP-D 的独特区室化。
Distinct compartmentalization of SP-A and SP-D in the vasculature and lungs of patients with idiopathic pulmonary fibrosis.
机构信息
Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
出版信息
BMC Pulm Med. 2014 Dec 8;14:196. doi: 10.1186/1471-2466-14-196.
BACKGROUND
Surfactant proteins SP-A and SP-D are useful biomarkers in diagnosis, monitoring, and prognosis of idiopathic pulmonary fibrosis (IPF). Despite their high structural homology, their serum concentrations often vary in IPF patients. This retrospective study aimed to investigate distinct compartmentalization of SP-A and SP-D in the vasculature and lungs by bronchoalveolar lavage fluid (BALF)/serum analysis, hydrophilicity and immunohistochemistry.
METHODS
We included 36 IPF patients, 18 sarcoidosis (SAR) patients and 20 healthy subjects. Low-speed centrifugal supernatants of BALF (Sup-1) were obtained from each subject. Sera were also collected from each patient. Furthermore, we separated Sup-1 of IPF patients into hydrophilic supernatant (Sup-2) and hydrophobic precipitate (Ppt) by high-speed centrifugation. We measured SP-A and SP-D levels of each sample with the sandwich ELISA technique. We analyzed the change of the BALF/serum level ratios of the two proteins in IPF patients and their hydrophilicity in BALF. The distribution in the IPF lungs was also examined by immunohistochemical staining.
RESULTS
In BALF, SP-A levels were comparable between the groups; however, SP-D levels were significantly lower in IPF patients than in others. Although IPF reduced the BALF/serum level ratios of the two proteins, the change in concentration of SP-D was more evident than SP-A. This suggests a higher disease impact for SP-D. Regarding hydrophilicity, although more than half of the SP-D remained in hydrophilic fractions (Sup-2), almost all of the SP-A sedimented in the Ppt with phospholipids. Hydrophilicity suggests that SP-D migrates into the blood more easily than SP-A in IPF lungs. Immunohistochemistry revealed that SP-A was confined to thick mucus-filling alveolar space, whereas SP-D was often intravascular. This data also suggests that SP-D easily leaks into the bloodstream, whereas SP-A remains bound to surfactant lipids in the alveolar space.
CONCLUSIONS
The current study investigated distinct compartmentalization of SP-A and SP-D in the vasculature and lungs. Our results suggest that serum levels of SP-D could reflect pathological changes of the IPF lungs more incisively than those of SP-A.
背景
表面活性蛋白 A（SP-A）和 D（SP-D）是特发性肺纤维化（IPF）诊断、监测和预后的有用生物标志物。尽管它们具有很高的结构同源性，但在 IPF 患者中，它们的血清浓度经常有所不同。这项回顾性研究旨在通过支气管肺泡灌洗液（BALF）/血清分析、亲水性和免疫组织化学来研究 SP-A 和 SP-D 在血管和肺部中的不同区室化。
方法
我们纳入了 36 名 IPF 患者、18 名结节病（SAR）患者和 20 名健康对照者。从每位受试者中获得 BALF 的低速离心上清液（Sup-1）。还从每位患者收集血清。此外，我们通过高速离心将 IPF 患者的 Sup-1 分离为亲水性上清液（Sup-2）和疏水性沉淀（Ppt）。我们使用夹心 ELISA 技术测量每个样本的 SP-A 和 SP-D 水平。我们分析了 IPF 患者 BALF/血清水平比值的变化及其在 BALF 中的亲水性。还通过免疫组织化学染色检查了 IPF 肺部的分布。
结果
在 BALF 中，各组之间 SP-A 水平相当；然而，IPF 患者的 SP-D 水平明显低于其他组。尽管 IPF 降低了两种蛋白质的 BALF/血清水平比值，但 SP-D 浓度的变化比 SP-A 更明显。这表明 SP-D 对疾病的影响更大。关于亲水性，尽管超过一半的 SP-D 仍留在亲水性部分（Sup-2），但几乎所有的 SP-A 都与磷脂一起沉淀在 Ppt 中。亲水性表明 SP-D 在 IPF 肺部中比 SP-A 更容易进入血液。免疫组织化学显示 SP-A 局限于充满厚黏液的肺泡空间，而 SP-D 通常位于血管内。这一数据还表明，SP-D 容易漏入血液，而 SP-A 则仍与肺泡空间中的表面活性剂脂质结合。
结论
本研究探讨了 SP-A 和 SP-D 在血管和肺部中的不同区室化。我们的结果表明，SP-D 的血清水平可能比 SP-A 更能准确反映 IPF 肺部的病理变化。
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