Immunophenotyping and protein profiling of Fontan-associated plastic bronchitis airway casts.
Immunophenotyping and protein profiling of Fontan-associated plastic bronchitis airway casts.
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DOI：
10.1513/annalsats.201209-080oc
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发表时间：
2013-04-01
影响因子：
8.3
通讯作者：
Stringer, Kathleen A
中科院分区：
文献类型：
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作者：
Racz, Jennifer;Mane, Gerta;Stringer, Kathleen A
依据：可塑性支气管炎（PB）是一种罕见且致命的疾病，其特征在于气道管型的形成。它最常发生在患有基础先天性心脏病的儿童中，这些先天性心脏病已通过Fontan手术得到缓解。Fontan循环导致高于正常的中心静脉压，并且已经假设气道管型的形成是由于淋巴漏。可塑性支气管炎发病机制的知识是穷人，主要源于已发表的病例reports. Adjectives：为了收集有关管型发病机制的信息，通过表征现有福尔马林保存，石蜡包埋的样品中的炎性细胞表型，并产生气道管型匀浆的蛋白质和趋化因子谱。我们使用了免疫荧光共聚焦显微镜，最先进的蛋白质组学，和细胞因子阵列分析，以免疫表型细胞内容物，并产生蛋白质和细胞因子的塑料支气管炎气道管型，分别。在管型样本中鉴定出中性粒细胞、嗜酸性粒细胞、巨噬细胞和B淋巴细胞; T淋巴细胞明显较少。纤维蛋白原是管型蛋白质组中含量丰富的蛋白质。组蛋白H4也很丰富，免疫荧光显微镜显示它主要是细胞外的。塑料支气管炎管的细胞因子的配置文件是proinflammatory.CONCLUSIONS：塑料支气管炎气道管与Fontan生理学的儿童是由纤维蛋白和细胞和炎症的性质，提供的证据表明，它们的形成不能简单地解释淋巴液泄漏到气道。细胞坏死的后果包括细胞外组蛋白和明显的低数量T细胞表明炎症消退的紊乱可能有助于管型形成。
RATIONALE: Plastic bronchitis (PB) is a rare and deadly condition that is characterized by the formation of airway casts. It most frequently occurs in children with underlying congenital heart disease that has been surgically palliated by the Fontan procedure. The Fontan circulation results in above-normal central venous pressure, and it has been hypothesized that the formation of airway casts is due to lymph leak. Knowledge of plastic bronchitis pathogenesis is poor and stems mostly from published case reports.OBJECTIVES: To garner information about cast pathogenesis by characterizing inflammatory cell phenotypes in existing formalin-preserved, paraffin-embedded samples and generating protein and cytokine-chemokine profiles of airway cast homogenates.METHODS: We used immunofluorescence confocal microscopy, state-of-the-science proteomics, and a cytokine array assay to immunophenotype cellular content and to generate protein and cytokine profiles of plastic bronchitis airway casts, respectively.MEASUREMENTS AND MAIN RESULTS: Neutrophils, eosinophils, macrophages, and B lymphocytes were identified in cast samples; there were notably fewer T lymphocytes. Fibrin(ogen) was an abundant protein in the cast proteome. Histone H4 was also abundant, and immunofluorescence microscopy demonstrated it to be mostly extracellular. The cytokine profile of plastic bronchitis casts was proinflammatory.CONCLUSIONS: Plastic bronchitis airway casts from children with Fontan physiology are composed of fibrin and are cellular and inflammatory in nature, providing evidence that their formation cannot be explained simply by lymph leak into the airways. Consequences of cellular necrosis including extracellular histones and the apparent low number of T cells indicate that a derangement in inflammation resolution likely contributes to cast formation.