Background. Lung transplantation has been performed worldwide and admitted as an effective treatment for patients with various end-stage lung diseases. However, limit reliable clinical indicators exist to identify patients at high risk for allograft failure in lung transplant recipients. The recent advances in the knowledge of immunological aspects of the pulmonary diseases, for that innate macrophage activation, are induced by pathogen or pathogen-derived molecules and widely accepted as the critical evidence among the pathogenesis of lung inflammation and fibrosis. This study was aimed at evaluating the clinical significance of CD86- and macrophage scavenger receptor 1- (MSR1-) positive cells during the development of idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH), and their potential roles in the prediction of the outcomes after lung transplantation were examined. Methods. Tissues from lung transplantation for 37 IPF and 15 PAH patients from the Department of Cardiothoracic Surgery in Wuxi People’s Hospital from December 2015 to December 2016 were analyzed by immunohistochemistry (IHC) for detecting the expression and CD86 and MSR1 and correlated with clinical events after lung transplantation. Results. IHC results showed that the expression of MSR1, IL-13, and arginase-1 (Arg1) but not CD86 in the lung section of IPF patients was dramatically enhanced when compared with that of PAH patients. The expression of MSR1, IL-13, and Arg1 but not CD86 in the lung from IPF patients with smoking was significantly increased when compared with that from nonsmoking subjects. In addition, the expression of MSR1-positive cells in IPF subjects with Klebsiella pneumoniae infection was dramatically enhanced than that in noninfection subjects. MSR1-positive macrophages were negatively associated with FEV1 and with FVC but not associated with TLC and with TL_CO. However, CD86-positive macrophages were not significantly associated with the above lung function-related factors. Furthermore, MSR1 had a higher area under the ROC curve (AUC) than CD86 for IPF diagnosis. Survival analysis indicated that high levels of MSR1-positive macrophages had a worse prognostic effect for IPF patients with lung transplantation. Conclusion. Our study indicates the clinical significance of Klebsiella pneumoniae infection-related MSR1-positive cells in IPF progression, and it could be a prognostic marker in IPF after the lung transplant; development strategies to reduce the expression of MSR1-positive macrophages in IPF may be beneficial for the lung transplant.

中文翻译：

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高表达巨噬细胞清除受体 1 预测特发性肺纤维化疾病移植患者的严重临床结果

背景. 肺移植已在世界范围内进行，并被认为是治疗各种终末期肺病患者的有效方法。然而，用于识别肺移植受者中同种异体移植失败高风险患者的可靠临床指标有限。肺部疾病免疫学方面的最新进展，即先天性巨噬细胞活化，是由病原体或病原体衍生分子诱导的，并被广泛接受为肺部炎症和纤维化发病机制中的关键证据。本研究旨在评估 CD86- 和巨噬细胞清除受体 1- (MSR1-) 阳性细胞在特发性肺纤维化 (IPF) 和肺动脉高压 (PAH) 发展过程中的临床意义，方法。对2015年12月至2016年12月无锡市人民医院心胸外科37例IPF和15例肺动脉高压患者的肺移植组织进行免疫组织化学（IHC）分析，检测CD86和MSR1的表达，并与肺移植后的临床事件相关. 结果。IHC 结果显示，与 PAH 患者相比，IPF 患者肺切片中 MSR1、IL-13 和 arginase-1 (Arg1) 而非 CD86 的表达显着增强。与不吸烟受试者相比，吸烟 IPF 患者肺中 MSR1、IL-13 和 Arg1 而非 CD86 的表达显着增加。此外，IPF 受试者中 MSR1 阳性细胞的表达肺炎克雷伯菌感染比非感染对象显着增强。MSR1 阳性巨噬细胞与 FEV1 和 FVC 呈负相关，但与 TLC 和 TL _CO无关。然而，CD86阳性巨噬细胞与上述肺功能相关因素无显着相关性。此外，对于 IPF 诊断，MSR1 的 ROC 曲线下面积 (AUC) 高于 CD86。生存分析表明，高水平的 MSR1 阳性巨噬细胞对 IPF 肺移植患者的预后影响更差。结论。我们的研究表明肺炎克雷伯菌的临床意义IPF进展中感染相关的MSR1阳性细胞，它可能是肺移植后IPF的预后标志物；降低 IPF 中 MSR1 阳性巨噬细胞表达的开发策略可能对肺移植有益。