Bioactive lipids in emphysema. Decoding fat to reveal COPD phenotypes.
Bioactive lipids in emphysema. Decoding fat to reveal COPD phenotypes.
复制标题
肺气肿中的生物活性脂质。
DOI：
10.1164/rccm.201412-2264ed
复制
发表时间：
2015
影响因子：
24.7
通讯作者：
Kheradmand,Farrah
中科院分区：
文献类型：
--
作者：
Mirzaie,Mehdi;Kheradmand,Farrah
令人欣慰的是，在21世纪，慢性阻塞性肺疾病（COPD）被恰当地认为不是单一疾病，而是具有几种不同表型的异质性肺部疾病群（1,2）。考虑到脂质及其生物活性代谢物如何在所有生物体中提供必要的结构和功能支持（例如，参与细胞增殖、凋亡、衰老、迁移和器官血管形成），它们在COPD复杂病理生物学中的作用被积极研究也就不足为奇了。具体而言，在不同类型的脂质中，鞘脂已被强调为COPD的关键生物活性代谢物和潜在生物标志物(3)。神经酰胺（Cer）、鞘磷脂（SM）和鞘鞘苷-1-磷酸（S1P）是最常见的生物活性脂质介质，其中一些作为g蛋白偶联受体的细胞外配体(4)。S1P及其受体S1PR1（在淋巴细胞上表达）已被证明是正常情况下细胞从淋巴系统向组织迁移所必需的(5)。s1p介导的梯度形成和淋巴细胞运输的发现刺激了新型治疗药物（如fingolimod）的发展，这些药物可以抑制免疫系统并治疗一些最顽固的自身免疫性炎症疾病(6)。S1P或其他生物活性脂质是否特异性地促进烟雾诱导的肺部炎症的获得性免疫反应，以及它们的调节是否可以用作不同COPD表型的新疗法，目前尚不清楚。
It is reassuring to know that in the 21st century, chronic obstructive pulmonary disease (COPD) is appropriately recognized not as a single disease but as a constellation of heterogeneous lung diseases with several distinct phenotypes (1, 2). Given how lipids and their bioactive metabolites provide essential structural and functional support in all living organisms (eg, participating in cellular proliferation, apoptosis, senescence, migration, and organ vascularization), it is not surprising that their role has been actively investigated in the complex pathobiology of COPD. Specifically, among different classes of lipids, sphingolipids have been highlighted as key bioactive metabolites and potential biomarkers in COPD (3).Ceramides (Cer), sphingomyelins (SM), and sphingosine-1-phosphate (S1P) are among the most common bioactive lipid mediators, some of which act as the extracellular ligands for G-protein-coupled receptors (4). S1P and its receptor, S1PR1 (expressed on lymphocytes), have been shown to be required for cell egression from the lymphoid system and into tissue under normal conditions (5). The discovery of S1P-mediated gradient formation and lymphocyte trafficking has stimulated the development of novel therapeutic agents (eg, fingolimod) that suppress the immune system and treat some of the most recalcitrant autoimmune inflammatory diseases (6). Whether S1P or other bioactive lipids specifically promote acquired immune responses in smoke-induced lung inflammation, and whether their modulation could be used as novel therapeutics in different COPD phenotypes, remains unclear.