School of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, UK.
Can Respir J. 2023 Jan 18;2023:1522593. doi: 10.1155/2023/1522593. eCollection 2023.
Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by excessive deposition of extracellular matrix in the interstitial lung parenchyma, often manifested by dyspnea and progressive loss of lung function. The role of inflammation in the pathogenesis of IPF is not well understood. This study evaluated the histopathological and inflammatory components of bleomycin-induced pulmonary fibrosis in mouse and sheep models, in terms of their ability to translate to the human IPF. Merino sheep ( = 8) were bronchoscopically administered with two bleomycin infusions, two weeks apart, into a caudal lung segment, with a saline (control) administered into a caudal segment in the opposite lung. Balb/c mice were twice intranasally instilled, one week apart, with either bleomycin ( = 7); or saline (control, = 7). Lung samples were taken for the histopathological assessment 28 days in sheep and 21 days in mice after the first bleomycin administration. We observed tertiary lymphoid aggregates, in the fibrotic lung parenchyma of sheep, but not in mouse lung tissues exposed to bleomycin. B-cell and T-cell infiltration significantly increased in sheep lung tissues compared to mouse lung tissues due to bleomycin injury. Statistical analysis showed that the fibrotic score, fibrotic fraction, and tissue fraction significantly increased in sheep lung tissues compared to murine lung tissues. The presence of tertiary lymphoid aggregates in the lung parenchyma and increased infiltration of T-cells and B-cells, in the sheep model, may be useful for the future study of the underlying inflammatory disease mechanisms in the lung parenchyma of IPF patients.
特发性肺纤维化（IPF）是一种以肺间质实质中细胞外基质过度沉积为特征的慢性疾病，常表现为呼吸困难和肺功能进行性丧失。炎症在 IPF 发病机制中的作用尚不清楚。本研究评估了博来霉素诱导的小鼠和绵羊肺纤维化模型中的组织病理学和炎症成分，以评估其在人类 IPF 中的转化能力。8 只美利奴绵羊通过支气管镜将两次博来霉素注入相隔两周的肺后段，在对侧肺的后段给予生理盐水（对照）。7 只 Balb/c 小鼠相隔一周两次经鼻腔给予博来霉素或生理盐水（对照）。在第一次博来霉素给药后 28 天的绵羊和 21 天的小鼠中，采集肺组织进行组织病理学评估。我们观察到，在绵羊的纤维化肺实质中存在三级淋巴样聚集物，但在暴露于博来霉素的小鼠肺组织中没有。与小鼠肺组织相比，由于博来霉素损伤，绵羊肺组织中 B 细胞和 T 细胞浸润显著增加。统计分析显示，与小鼠肺组织相比，绵羊肺组织的纤维化评分、纤维化分数和组织分数显著增加。在绵羊模型中，肺实质中存在三级淋巴样聚集物和 T 细胞和 B 细胞的浸润增加，可能有助于未来研究 IPF 患者肺实质中潜在的炎症性疾病机制。
