关于哮喘气道炎症的解决途径
2018/03/05
摘要
哮喘是一种慢性疾病，其特征在于气道持续性炎症，伴粘膜嗜酸性粒细胞、T淋巴细胞、肥大细胞浸润和促炎细胞因子、脂质介质释放。气道炎症的自然消退现在被认为是主动的宿主反应，其中内源性促分解介质的调控为高度协调的细胞事件，所述介质能够使组织体内平衡得以恢复。促分裂介质的主要成员是由必需多不饱和脂肪酸（包括花生四烯酸衍生的脂氧素，二十碳五烯酸衍生的E系列消退素以及二十二碳六烯酸衍生的D系列消退素，保护素和抗炎介质maresins）酶促衍生而来。在功能上，这些专门的促分解介质可以限制更多的白细胞募集，诱导粒细胞凋亡，并增强巨噬细胞的细胞吞噬作用。它们还可以将巨噬细胞转变为活化状态，促进非凋亡细胞返回淋巴管和血管，并帮助启动组织修复和愈合。在这篇综述中，我们重点介绍了成功消退炎症的细胞和分子机制，并描述了驱动这些过程的主要促分解介质。此外，我们最近报道的数据表明，严重哮喘的病理学改变可能导致了气道炎症消退受损，包括这些促分解介质的合成缺陷。最后，我们讨论了治疗的展望。
Towards targeting resolution pathways of airway inflammation in asthma.
Barnig C, Frossard N, Levy BD.
Abstract
Asthma is a chronic disorder characterized by persistent inflammation of the airways with mucosal infiltration of eosinophils, T lymphocytes, and mast cells, and release of proinflammatory cytokines and lipid mediators. The natural resolution of airway inflammation is now recognized as an active host response, with highly coordinated cellular events under the control of endogenous pro-resolving mediators that enable the restoration of tissue homeostasis. Lead members of proresolving mediators are enzymatically derived from essential polyunsaturated fatty acids, including arachidonic acid-derived lipoxins, eicosapentaenoic acid-derived E-series resolvins, and docosahexaenoic acid-derived D-series resolvins, protectins, and maresins. Functionally, these specialized pro-resolving mediators can limit further leukocyte recruitment, induce granulocyte apoptosis, and enhance efferocytosis by macrophages. They can also switch macrophages from classical to alternatively activated cells, promote the return of non-apoptotic cells to lymphatics and blood vessels, and help initiate tissue repair and healing. In this review, we highlight cellular and molecular mechanisms for successful resolution of inflammation, and describe the main specialized pro-resolving mediators that drive these processes. Furthermore, we report recent data suggesting that the pathobiology of severe asthma may result in part from impaired resolution of airway inflammation, including defects in the biosynthesis of these specialized pro-resolving mediators. Finally, we discuss resolution-based therapeutic perspectives.
哮喘是一种慢性疾病，其特征在于气道持续性炎症，伴粘膜嗜酸性粒细胞、T淋巴细胞、肥大细胞浸润和促炎细胞因子、脂质介质释放。气道炎症的自然消退现在被认为是主动的宿主反应，其中内源性促分解介质的调控为高度协调的细胞事件，所述介质能够使组织体内平衡得以恢复。促分裂介质的主要成员是由必需多不饱和脂肪酸（包括花生四烯酸衍生的脂氧素，二十碳五烯酸衍生的E系列消退素以及二十二碳六烯酸衍生的D系列消退素，保护素和抗炎介质maresins）酶促衍生而来。在功能上，这些专门的促分解介质可以限制更多的白细胞募集，诱导粒细胞凋亡，并增强巨噬细胞的细胞吞噬作用。它们还可以将巨噬细胞转变为活化状态，促进非凋亡细胞返回淋巴管和血管，并帮助启动组织修复和愈合。在这篇综述中，我们重点介绍了成功消退炎症的细胞和分子机制，并描述了驱动这些过程的主要促分解介质。此外，我们最近报道的数据表明，严重哮喘的病理学改变可能导致了气道炎症消退受损，包括这些促分解介质的合成缺陷。最后，我们讨论了治疗的展望。
(中日友好医院呼吸与危重症医学科 王圆方 摘译 林江涛 审校)
(Pharmacol Ther. 2018 Jan 19. pii: S0163-7258(18)30011-1.)
(Pharmacol Ther. 2018 Jan 19. pii: S0163-7258(18)30011-1.)
Towards targeting resolution pathways of airway inflammation in asthma.
Barnig C, Frossard N, Levy BD.
Abstract
Asthma is a chronic disorder characterized by persistent inflammation of the airways with mucosal infiltration of eosinophils, T lymphocytes, and mast cells, and release of proinflammatory cytokines and lipid mediators. The natural resolution of airway inflammation is now recognized as an active host response, with highly coordinated cellular events under the control of endogenous pro-resolving mediators that enable the restoration of tissue homeostasis. Lead members of proresolving mediators are enzymatically derived from essential polyunsaturated fatty acids, including arachidonic acid-derived lipoxins, eicosapentaenoic acid-derived E-series resolvins, and docosahexaenoic acid-derived D-series resolvins, protectins, and maresins. Functionally, these specialized pro-resolving mediators can limit further leukocyte recruitment, induce granulocyte apoptosis, and enhance efferocytosis by macrophages. They can also switch macrophages from classical to alternatively activated cells, promote the return of non-apoptotic cells to lymphatics and blood vessels, and help initiate tissue repair and healing. In this review, we highlight cellular and molecular mechanisms for successful resolution of inflammation, and describe the main specialized pro-resolving mediators that drive these processes. Furthermore, we report recent data suggesting that the pathobiology of severe asthma may result in part from impaired resolution of airway inflammation, including defects in the biosynthesis of these specialized pro-resolving mediators. Finally, we discuss resolution-based therapeutic perspectives.
上一篇：
健康人群和哮喘队列参与者基于测定肺功能波动测定显示的功能表型
下一篇：
低密度脂蛋白受体相关蛋白1通过抑制树突状细胞介导的适应性免疫应答来减弱屋尘螨诱导的嗜酸性气道炎症
