Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells.
Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells.
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非特异性间质性肺炎中的肺泡血管重塑：用 COL15A1 阳性内皮细胞替换正常肺毛细血管。
DOI：
10.1164/rccm.202303-0544le
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发表时间：
2023
影响因子：
24.7
通讯作者：
Yale-MHH-MGHStudyGroup
中科院分区：
文献类型：
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作者：
Schupp,JonasC;Manning,EdwardP;Chioccioli,Maurizio;Kamp,JanC;Christian,Leonard;Ryu,Changwan;Herzog,Erica;Kühnel,MarkP;Prasse,Antje;Kaminski,Naftali;Jonigk,DannyD;Homer,RobertJ;Yale-MHH-MGHStudyGroup
方法本研究包括来自耶鲁大学的确诊fNSIP患者的六个诊断性手术肺活检样本和在汉诺威医学院（MHH）肺移植期间获得的患有终末期fNSIP的患者的六个人肺外植体（对于基本患者特征，参见表1）。九个非纤维化对照组来自肺移植期间的手术大小调整或手术切除的组织学无肿瘤标本。获得了相关伦理委员会的批准（MHH编号2702-2015，Yale 2000031225）。使用已建立的染色方案和已建立的染色组，通过免疫荧光显微镜评价内皮成分，如其他地方所述（6）。四个目标染色：气细胞特异性HPGD，泛毛细血管PRX，纤维化内皮细胞的COL 15 A1和泛内皮CD 31。使用ImageJ的ImageJ颜色阈值函数分析感兴趣区域，选择的颜色对应于感兴趣的靶蛋白。通过排除大气道和大血管，我们将分析重点放在肺实质上。使用随机选择的单独感兴趣区域对每个样本进行分析，并对每个样本进行9次重复内膜直径和壁厚测量，报告样本的平均值。使用Mann-Whitney U检验比较数值。P值< 0.05被认为是显著的。
MethodsSix diagnostic surgical lung biopsy samples of patients with confirmed fNSIP from Yale University and six human lung explants of patients with end-stage fNSIP obtained during lung transplantation at Hannover Medical School (MHH) were included in this study (for basic patient characteristics, see Table 1). The nine nonfibrotic controls were obtained from either surgical size adjustment during lung transplantation or histologically tumor-free specimens from surgical cancer resections. Approval of the relevant ethics committees was obtained (MHH number 2702-2015, Yale 2000031225). Endothelial composition was evaluated by immunofluorescent microscopy using an established staining protocol and established staining panels as described elsewhere (6). Four targets were stained: aerocyte-specific HPGD, pancapillary PRX, COL15A1 for fibrotic endothelial cells, and panendothelial CD31. Regions of interest were analyzed using the ImageJ color threshold function of ImageJ, with the chosen color corresponding to the targeted protein of interest. We focused our analysis on the lung parenchyma by excluding large airways and large vessels. Randomly selected separate regions of interest were used for analyses within each sample, and nine replicates of intimal diameter and wall thickness measurements were made for each sample, with the mean for the sample reported. Values were compared using the Mann-Whitney U test. P values< 0.05 were considered significant.