Persson Hans Lennart, Sioutas Apostolos, Jacobson Petra, Vainikka Linda K
Department of Respiratory Medicine in Linköping, Linköping University, Linköping, Sweden.
Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
J Inflamm Res. 2020 Nov 16;13:925-932. doi: 10.2147/JIR.S280419. eCollection 2020.
The lung macrophage (LM) is involved in most inflammatory processes of the human lung by clearance of dying cells and by wound repair. Upon cellular stress by oxidant challenge in vivo lysosomes may rupture in LMs and leakage of cellular content and cell debris may trigger airway inflammation and fibrosis, which may lead to chronic airflow limitation (CAL).
The aim of this study was to determine whether lysosomal membrane permeabilization (LMP) in LMs challenged to oxidants ex vivo is associated with airway inflammation and CAL, the latter assessed as the reduced forced expiratory volume in one second (FEV) expressed as % of predicted.
Twenty-eight subjects were investigated; 13 lung-healthy subjects and 15 subjects with a variety of inflammatory disorders, demonstrating CAL on dynamic spirometry (defined as an FEV/FVC ratio < 0.70). LMs were harvested by broncho-alveolar lavage (BAL) and challenged ex vivo by oxidants. LMP in oxidant-exposed LMs was assessed as the emitted acridine orange (AO) green fluorescence from oxidant-exposed LMs (using macrophage-like murine J774 cells as positive controls). Inflammatory cells in BAL were counted and lung volumes were recorded.
Oxidant-induced LMP in LMs was significantly greater among subjects with CAL and particularly among those with ongoing inflammation. Previous tobacco history did not influence LMP. Among subjects with CAL, oxidant-induced LMP correlated negatively with FEV% of predicted.
Lysosomes of LMs harvested from patients with CAL demonstrate an increased sensitivity to oxidants, which may trigger mechanisms behind CAL, eg, chronic airway inflammation and fibrotic re-modelling. The study suggests a mechanistic role for LMP in LMs on airway inflammation, suggesting an anti-inflammatory effect by drugs that prevent increased LMP.
肺巨噬细胞（LM）通过清除死亡细胞和伤口修复参与人类肺部的大多数炎症过程。在体内受到氧化剂攻击导致细胞应激时，溶酶体可能在肺巨噬细胞中破裂，细胞内容物和细胞碎片的泄漏可能引发气道炎症和纤维化，进而导致慢性气流受限（CAL）。
本研究旨在确定体外受到氧化剂攻击的肺巨噬细胞中的溶酶体膜通透性（LMP）是否与气道炎症和慢性气流受限相关，后者通过以预测值的百分比表示的一秒用力呼气量（FEV）降低来评估。
对28名受试者进行了研究；13名肺部健康受试者和15名患有各种炎症性疾病的受试者，这些受试者在动态肺量计检查中表现出慢性气流受限（定义为FEV/FVC比值<0.70）。通过支气管肺泡灌洗（BAL）收集肺巨噬细胞，并在体外受到氧化剂攻击。将暴露于氧化剂的肺巨噬细胞中的LMP评估为暴露于氧化剂的肺巨噬细胞发出的吖啶橙（AO）绿色荧光（使用巨噬细胞样小鼠J774细胞作为阳性对照）。对支气管肺泡灌洗中的炎症细胞进行计数并记录肺容积。
在患有慢性气流受限的受试者中，尤其是在那些有持续炎症的受试者中，氧化剂诱导的肺巨噬细胞中的LMP明显更高。既往吸烟史不影响LMP。在患有慢性气流受限的受试者中，氧化剂诱导的LMP与预测的FEV%呈负相关。
从患有慢性气流受限的患者中收集的肺巨噬细胞的溶酶体对氧化剂的敏感性增加，这可能触发慢性气流受限背后的机制，例如慢性气道炎症和纤维化重塑。该研究表明LMP在肺巨噬细胞对气道炎症的作用机制中发挥作用，提示通过预防LMP增加的药物具有抗炎作用。
