Digital Imaging Analysis Reveals Reduced Alveolar α-Smooth Muscle Actin Expression in Severe Asthma.
Digital Imaging Analysis Reveals Reduced Alveolar α-Smooth Muscle Actin Expression in Severe Asthma.
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DOI：
10.1097/pai.0000000000000926
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发表时间：
2021-08-01
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影响因子：
--
通讯作者：
Trejo Bittar HE
中科院分区：
文献类型：
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作者：
Jerome JA;Wenzel SE;Trejo Bittar HE
α-平滑肌肌动蛋白(α-SMA)表达的大气道平滑肌扩张在哮喘中已有较好的研究。然而，在更远端的肺泡实质中表达α-SMA的细胞，包括肺泡间隔内的周细胞和肌纤维母细胞，在哮喘的病理生理学中的作用仍然相对未知。本研究的目的是评估α-SMA在重度哮喘患者肺泡实质中的表达，并与健康对照组或慢性阻塞性肺疾病患者进行比较。应用定量数字图像分析和电视胸镜手术(VATS)肺活检，我们发现重度哮喘患者肺泡实质α-SMA的表达显著低于健康对照组(平均阳性像素百分比：12%vs.23%，p=0.005)。与对照组相比，慢性阻塞性肺疾病患者α-SMA的阳性表达有相似但有趋势的下降(平均%阳性：17%对23%，p=0.107)，这可能提示α-SMA的表达缺失是阻塞性肺疾病的一种共性。重度哮喘组与对照组(平均阳性核百分率：34%比42%，p=0.218)的ERG染色相似，这表明毛细血管内皮细胞和可能完整的毛细血管相关的α-SMA阳性周细胞。这些发现提示，重症哮喘患者α-SMA的表达缺失可能是由于肌成纤维细胞α-SMA的表达或细胞数量的改变所致。有必要进行进一步研究，以充分评估这一现象的可能机制和后果。
Expansion of α-smooth muscle actin(α-SMA)-expressing airway smooth muscle of the large airways in asthma is well-studied. However, the contribution of α-SMA-expressing cells in the more distal alveolated parenchyma, including pericytes and myofibroblasts within the alveolar septum, to asthma pathophysiology remains relatively unexplored. The objective of this study was to evaluate α-SMA expression in the alveolated parenchyma of individuals with severe asthma, compared to healthy controls or individuals with chronic obstructive pulmonary disease (COPD). Using quantitative digital image analysis and video-assisted thoracoscopic surgery (VATS) lung biopsies, we show that alveolated parenchyma α-SMA expression is markedly reduced in severe asthma in comparison to healthy controls (mean %positive pixels: 12% vs. 23%, p=0.005). COPD cases showed a similar, but trending, decrease in α-SMA positivity compared to controls (mean %positivity: 17% vs. 23%, p=0.107), which may suggest loss of α SMA expression is a commonality of obstructive lung diseases. The severe asthma group had similar staining for ERG, a specific endothelial marker, comparatively to controls (mean %positive nuclei: 34% vs. 42%, p=0.218), which suggests intact capillary endothelium and likely intact capillary-associated, α-SMA-positive pericytes. These findings suggest that the loss of α-SMA expression in severe asthma may be due to changes in myofibroblast α-SMA expression or cell number. Further study is necessary to fully evaluate possible mechanisms and consequences of this phenomenon.