Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan; Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan.
Biochem Biophys Res Commun. 2024 Jan 29;694:149419. doi: 10.1016/j.bbrc.2023.149419. Epub 2023 Dec 21.
Increasing evidence indicates that bioactive lipid mediators are involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Recently, glycero-lysophospholipids, such as lysophosphatidic acid (LysoPA) and lysophosphatidylserine (LysoPS), have been recognized as significant inflammation-related lipid mediators. However, their association with COPD remains unclear.
We used an elastase-induced murine emphysema model to analyze the levels of lysophospholipids and diacyl-phospholipids in the lungs. Additionally, we assessed the expression of LysoPS-related genes and published data on smokers.
In the early phase of an elastase-induced murine emphysema model, the levels of LysoPS and its precursor (phosphatidylserine [PS]) were significantly reduced, without significant modulations in other glycero-lysophospholipids. Additionally, there was an upregulation in the expression of lysoPS receptors, specifically GPR34, observed in the lungs of a cigarette smoke-exposed mouse model and the alveolar macrophages of human smokers. Elastase stimulation induces GPR34 expression in a human macrophage cell line in vitro.
Elastase-induced lung emphysema affects the LysoPS/PS-GPR34 axis, and cigarette smoking or elastase upregulates GPR34 expression in alveolar macrophages. This novel association may serve as a potential pharmacological target for COPD treatment.
越来越多的证据表明，生物活性脂质介质参与了慢性阻塞性肺疾病（COPD）的发病机制。最近，甘油磷酸脂，如溶血磷脂酸（LysoPA）和溶血磷脂酰丝氨酸（LysoPS），已被认为是重要的与炎症相关的脂质介质。然而，它们与 COPD 的关系尚不清楚。
我们使用弹性蛋白酶诱导的小鼠肺气肿模型来分析肺中溶血磷脂和二酰基磷脂的水平。此外，我们评估了 LysoPS 相关基因的表达和吸烟者的发表数据。
在弹性蛋白酶诱导的小鼠肺气肿模型的早期阶段，LysoPS 及其前体（磷脂酰丝氨酸[PS]）的水平显著降低，而其他甘油磷酸脂没有明显的变化。此外，在香烟烟雾暴露的小鼠模型的肺和人类吸烟者的肺泡巨噬细胞中观察到 LysoPS 受体（特别是 GPR34）的表达上调。弹性蛋白酶刺激在体外诱导人巨噬细胞系中 GPR34 的表达。
弹性蛋白酶诱导的肺肺气肿影响 LysoPS/PS-GPR34 轴，香烟烟雾或弹性蛋白酶上调肺泡巨噬细胞中的 GPR34 表达。这种新的关联可能成为 COPD 治疗的潜在药物靶点。
