成纤维细胞形成的纤维胶原组织缺陷导致哮喘患者气道重塑
2020/02/11
摘要
基本原理:组织学染色已被用作观察哮喘患者气道重塑相关的细胞外基质(ECM)变化的金标准，但它们没有提供ECM的生化和结构特征的信息，虽然这些信息对于理解组织功能的变化至关重要。
目的:演示使用非线性光学显微镜(NLOM)和结构分析算法来反映纤维胶原蛋白(二次谐波产生)和弹性蛋白(双光子激发自荧光)，以获得哮喘患者重建的ECM环境的生化和结构信息。
方法:对哮喘(13例)和对照组(12例)非移植供体肺进行NLOM用于评估气道胶原蛋白和弹性蛋白纤维，提取肺纤维母细胞进行体外实验。
测量和主要结果:使用NLOM成像，与对照组相比，哮喘大气道和小气道中的纤维胶原不仅增加，而且高度紊乱和碎片化。此外，这种结构改变存在于患有哮喘的儿童和成人捐赠者，而与致命疾病无关。体外研究表明，哮喘患者的气道成纤维细胞在原纤维胶原蛋白i的包装方面存在缺陷，而其所表达的核心蛋白聚糖较少，而核心蛋白聚糖对胶原纤维的包装非常重要。使用透射电镜观察发现，与对照组相比，哮喘患者气道内的胶原纤维包装更混乱。
结论:NLOM成像可以对ECM进行结构评估，这些数据表明哮喘气道重塑涉及到气道成纤维细胞对无组织的纤维胶原的逐渐积累。本研究强调了NLOM在体内评估气道重塑的潜在临床应用前景。
Mostaço-Guidolin LB, et al. Am J Respir Crit Care Med. 2019 Aug 15.
Abstract
Rationale: Histologic stains have been used as the gold standard to visualize extracellular matrix (ECM) changes associated with airway remodeling in asthma, yet they provide no information on the biochemical and structural characteristics of the ECM, which are vital to understanding alterations in tissue function.
Objectives: To demonstrate the use of nonlinear optical microscopy (NLOM) and texture analysis algorithms to image fibrillar collagen (second harmonic generation) and elastin (two-photon excited autofluorescence), to obtain biochemical and structural information on the remodeled ECM environment in asthma.
Methods: Nontransplantable donor lungs from donors with asthma (n = 13) and control (n = 12) donors were used for the assessment of airway collagen and elastin fibers by NLOM, and extraction of lung fibroblasts for in vitro experiments.
Measurements and Main Results: Fibrillar collagen is not only increased but also highly disorganized and fragmented within large and small asthmatic airways compared with control subjects, using NLOM imaging. Furthermore, such structural alterations are present in pediatric and adult donors with asthma, irrespective of fatal disease. In vitro studies demonstrated that asthmatic airway fibroblasts are deficient in their packaging of fibrillar collagen-I and express less decorin, important for collagen fibril packaging. Packaging of collagen fibrils was found to be more disorganized in asthmatic airways compared with control subjects, using transmission electron microscopy.
Conclusions: NLOM imaging enabled the structural assessment of the ECM, and the data suggest that airway remodeling in asthma involves the progressive accumulation of disorganized fibrillar collagen by airway fibroblasts. This study highlights the future potential clinical application of NLOM to assess airway remodeling in vivo.
基本原理:组织学染色已被用作观察哮喘患者气道重塑相关的细胞外基质(ECM)变化的金标准，但它们没有提供ECM的生化和结构特征的信息，虽然这些信息对于理解组织功能的变化至关重要。
目的:演示使用非线性光学显微镜(NLOM)和结构分析算法来反映纤维胶原蛋白(二次谐波产生)和弹性蛋白(双光子激发自荧光)，以获得哮喘患者重建的ECM环境的生化和结构信息。
方法:对哮喘(13例)和对照组(12例)非移植供体肺进行NLOM用于评估气道胶原蛋白和弹性蛋白纤维，提取肺纤维母细胞进行体外实验。
测量和主要结果:使用NLOM成像，与对照组相比，哮喘大气道和小气道中的纤维胶原不仅增加，而且高度紊乱和碎片化。此外，这种结构改变存在于患有哮喘的儿童和成人捐赠者，而与致命疾病无关。体外研究表明，哮喘患者的气道成纤维细胞在原纤维胶原蛋白i的包装方面存在缺陷，而其所表达的核心蛋白聚糖较少，而核心蛋白聚糖对胶原纤维的包装非常重要。使用透射电镜观察发现，与对照组相比，哮喘患者气道内的胶原纤维包装更混乱。
结论:NLOM成像可以对ECM进行结构评估，这些数据表明哮喘气道重塑涉及到气道成纤维细胞对无组织的纤维胶原的逐渐积累。本研究强调了NLOM在体内评估气道重塑的潜在临床应用前景。
（中国医科大学附属第一医院 李文扬 摘译 杨冬 审校）
（Mostaço-Guidolin LB, et al. Am J Respir Crit Care Med. 2019 Aug 15.）
Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma.（Mostaço-Guidolin LB, et al. Am J Respir Crit Care Med. 2019 Aug 15.）
Mostaço-Guidolin LB, et al. Am J Respir Crit Care Med. 2019 Aug 15.
Abstract
Rationale: Histologic stains have been used as the gold standard to visualize extracellular matrix (ECM) changes associated with airway remodeling in asthma, yet they provide no information on the biochemical and structural characteristics of the ECM, which are vital to understanding alterations in tissue function.
Objectives: To demonstrate the use of nonlinear optical microscopy (NLOM) and texture analysis algorithms to image fibrillar collagen (second harmonic generation) and elastin (two-photon excited autofluorescence), to obtain biochemical and structural information on the remodeled ECM environment in asthma.
Methods: Nontransplantable donor lungs from donors with asthma (n = 13) and control (n = 12) donors were used for the assessment of airway collagen and elastin fibers by NLOM, and extraction of lung fibroblasts for in vitro experiments.
Measurements and Main Results: Fibrillar collagen is not only increased but also highly disorganized and fragmented within large and small asthmatic airways compared with control subjects, using NLOM imaging. Furthermore, such structural alterations are present in pediatric and adult donors with asthma, irrespective of fatal disease. In vitro studies demonstrated that asthmatic airway fibroblasts are deficient in their packaging of fibrillar collagen-I and express less decorin, important for collagen fibril packaging. Packaging of collagen fibrils was found to be more disorganized in asthmatic airways compared with control subjects, using transmission electron microscopy.
Conclusions: NLOM imaging enabled the structural assessment of the ECM, and the data suggest that airway remodeling in asthma involves the progressive accumulation of disorganized fibrillar collagen by airway fibroblasts. This study highlights the future potential clinical application of NLOM to assess airway remodeling in vivo.
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哮喘中的嗜酸性粒细胞炎症及有缺陷的上皮细胞的翻译控制
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自然语言处理可促进基于EHR的过敏，哮喘和免疫学临床研究
