Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma
Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma
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DOI：
10.1164/rccm.201810-1855oc
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发表时间：
2019-08-15
影响因子：
24.7
通讯作者：
Hackett, Tillie-Louise
中科院分区：
文献类型：
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作者：
Mostaco-Guidolin, Leila B.;Osei, Emmanuel T.;Hackett, Tillie-Louise
基本原理：组织学染色已被用作观察与哮喘气道重塑相关的细胞外基质（ECM）变化的金标准，但它们不能提供ECM的生物化学和结构特征的信息，而这些信息对于理解组织功能的改变至关重要。目的：演示使用非线性光学显微镜（NLOM）和纹理分析算法对纤维胶原进行成像（二次谐波产生）和弹性蛋白（双光子激发的自体荧光），以获得哮喘中重塑的ECM环境的生化和结构信息。来自哮喘供体（n = 13）和对照供体（n = 12）的不可移植供体肺用于通过NLOM评估气道胶原和弹性蛋白纤维，测量和主要结果：使用NLOM成像，与对照受试者相比，在大的和小的哮喘气道内，原纤维胶原蛋白不仅增加，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供体中，而与致命疾病无关。体外研究表明，哮喘气道成纤维细胞缺乏其包装的纤维状胶原蛋白-I和表达较少的核心蛋白聚糖，重要的胶原纤维包装。胶原纤维的包装被发现是更混乱的哮喘气道与对照组相比，使用透射电子显微镜。结论：NLOM成像使ECM的结构评估，和数据表明，在哮喘气道重塑涉及无序的纤维胶原的气道成纤维细胞的逐步积累。这项研究强调了NLOM在体内评估气道重塑的未来潜在临床应用。
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 (twophoton 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.