Department of Cardiothoracic Surgery in Affiliated Wuxi People's Hospital, Wuxi, China.
Department of Dermatology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, China.
J Immunol Res. 2021 Jan 31;2021:6690100. doi: 10.1155/2021/6690100. eCollection 2021.
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.
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.
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 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. 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.
Our study indicates the clinical significance of 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.
肺移植已在全球范围内开展,并被认为是治疗各种终末期肺部疾病的有效方法。然而,目前尚无可靠的临床指标来识别肺移植受者中同种异体移植物失功风险较高的患者。近年来,人们对肺部疾病的免疫学方面的认识不断深入,先天巨噬细胞的激活是由病原体或病原体衍生的分子诱导的,被广泛认为是肺炎症和纤维化发病机制中的关键证据。本研究旨在评估 CD86 和巨噬细胞清道夫受体 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,并探讨其在预测肺移植后结局方面的潜在作用。
本研究分析了 2015 年 12 月至 2016 年 12 月在无锡市人民医院心胸外科进行肺移植的 37 例 IPF 和 15 例 PAH 患者的组织,通过免疫组化(IHC)检测 MSR1、白细胞介素 13(IL-13)和精氨酸酶 1(Arg1)的表达和 CD86 和 MSR1,并与肺移植后的临床事件相关联。
IHC 结果显示,与 PAH 患者相比,IPF 患者肺组织中 MSR1、IL-13 和 Arg1(但不是 CD86)的表达显著增强。与非吸烟患者相比,吸烟的 IPF 患者的 MSR1、IL-13 和 Arg1 表达显著增加。此外,在感染患者中,MSR1 阳性细胞的表达明显高于非感染患者。MSR1 阳性巨噬细胞与 FEV1 和 FVC 呈负相关,但与 TLC 和 TL 不相关。然而,CD86 阳性巨噬细胞与上述肺功能相关因素无显著相关性。此外,MSR1 对 IPF 的诊断具有更高的 ROC 曲线下面积(AUC)。生存分析表明,肺移植后 MSR1 阳性巨噬细胞水平高的 IPF 患者预后较差。
本研究表明,与感染相关的 MSR1 阳性细胞在 IPF 进展中的临床意义,并可能成为肺移植后 IPF 的预后标志物;减少 IPF 中 MSR1 阳性巨噬细胞表达的发展策略可能有益于肺移植。