成纤维细胞形成的纤维胶原组织缺陷有助于哮喘患者气道重塑
2019/05/10
摘要
背景：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，但它们没有提供有关ECM生化和结构特征的信息，而这对于了解组织功能的变化是至关重要的。展示非线性光学显微镜（NLOM）和纹理分析算法对纤维胶原（二次谐波产生）和弹性蛋白（双光子激发自发荧光）成像的应用，以获得哮喘重塑ECM环境的生化和结构信息。
方法：采用非移植性哮喘供体肺（n=13）和对照供体肺（n=12）进行NLOM下气道胶原和弹性蛋白纤维的测定，并提取肺成纤维细胞进行体外实验。
结果：与对照组相比，使用NLOM成像发现纤维胶原蛋白不仅增加，而且在大小哮喘气道中高度无序和碎片化。此外，这种结构变化存在于儿童和成人哮喘供体中，与致命疾病无关。体外研究表明，哮喘气道成纤维细胞缺乏纤维状胶原蛋白I的包装，并且表达较少的对胶原纤维包装很重要的核心蛋白聚糖。使用透射电子显微镜观察发现，与对照相比，在哮喘气道中胶原纤维的包装更加混乱。
结论：NLOM成像使ECM的结构评估成为可能，并且数据表明哮喘中的气道重塑涉及气道成纤维细胞逐渐积累的紊乱的纤维状胶原。该研究强调了NLOM在体内气道重塑评估中的潜在临床应用。
Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma.
Mostaço-Guidolin LB, Osei ET, Ullah J, Hajimohammadi S, Fouadi M, Li X, Li V, Shaheen F, Yang CX, Chu F, Cole DJ, Brandsma CA, Heijink IH, Maksym GN, Walker D, Hackett TL.
Abstract
BACKGROUND:Histological 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. Demonstrate the use of non-linear 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:Non-transplantable donor lungs from asthmatic (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.
RESULTS:Fibrillar collagen is not only increased, but highly disorganized and fragmented within large and small asthmatic airways compared to controls, using NLOM imaging. Further, such structural alterations are present in pediatric and adult asthmatic donors, 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 asthmatics airways compared to controls, 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.
背景：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，但它们没有提供有关ECM生化和结构特征的信息，而这对于了解组织功能的变化是至关重要的。展示非线性光学显微镜（NLOM）和纹理分析算法对纤维胶原（二次谐波产生）和弹性蛋白（双光子激发自发荧光）成像的应用，以获得哮喘重塑ECM环境的生化和结构信息。
方法：采用非移植性哮喘供体肺（n=13）和对照供体肺（n=12）进行NLOM下气道胶原和弹性蛋白纤维的测定，并提取肺成纤维细胞进行体外实验。
结果：与对照组相比，使用NLOM成像发现纤维胶原蛋白不仅增加，而且在大小哮喘气道中高度无序和碎片化。此外，这种结构变化存在于儿童和成人哮喘供体中，与致命疾病无关。体外研究表明，哮喘气道成纤维细胞缺乏纤维状胶原蛋白I的包装，并且表达较少的对胶原纤维包装很重要的核心蛋白聚糖。使用透射电子显微镜观察发现，与对照相比，在哮喘气道中胶原纤维的包装更加混乱。
结论：NLOM成像使ECM的结构评估成为可能，并且数据表明哮喘中的气道重塑涉及气道成纤维细胞逐渐积累的紊乱的纤维状胶原。该研究强调了NLOM在体内气道重塑评估中的潜在临床应用。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2019 Apr 5. doi: 10.1164/rccm.201810-1855OC. [Epub ahead of print])
(Am J Respir Crit Care Med. 2019 Apr 5. doi: 10.1164/rccm.201810-1855OC. [Epub ahead of print])
Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma.
Mostaço-Guidolin LB, Osei ET, Ullah J, Hajimohammadi S, Fouadi M, Li X, Li V, Shaheen F, Yang CX, Chu F, Cole DJ, Brandsma CA, Heijink IH, Maksym GN, Walker D, Hackett TL.
Abstract
BACKGROUND:Histological 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. Demonstrate the use of non-linear 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:Non-transplantable donor lungs from asthmatic (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.
RESULTS:Fibrillar collagen is not only increased, but highly disorganized and fragmented within large and small asthmatic airways compared to controls, using NLOM imaging. Further, such structural alterations are present in pediatric and adult asthmatic donors, 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 asthmatics airways compared to controls, 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.
上一篇：
肺计算模型和小气道在哮喘中的作用
下一篇：
哮喘中的细胞因子
