Carlo Troy, Levy Bruce D
Brigham and Women's Hospital, Boston, MA, USA.
Allergol Int. 2008 Dec;57(4):299-305. doi: 10.2332/allergolint.08-RAI-0018. Epub 2008 Nov 1.
Asthma pathobiology is remarkable for chronic airway inflammation that fails to spontaneously resolve. No curative therapy is currently available. A growing body of evidence indicates that, in health, inflammation resolution is an active process orchestrated by specific chemical mediators that are elaborated to restore tissue homeostasis. Activated cell membranes release polyunsaturated fatty acids from phospholipids for enzymatic conversion to biologically active mediators with profound regulatory effects on innate and adaptive immunity. Some of these mediators carry anti-inflammatory and pro-resolving actions that are transduced in a cell-type specific manner via specific recognition sites that initiate regulatory intracellular signals, such as presqualene diphosphate remodeling, to limit pro-phlogistic cell activation. Some of these counter-regulatory lipid mediators have been identified in the airway during asthma and defects in their production are associated with disease severity. In this review, we describe the biosynthesis and bioactions of pro-resolving chemical mediators and provide examples of select mediators and their structural analogs with particular relevance to asthma.
哮喘病理生物学的显著特征是慢性气道炎症无法自发消退。目前尚无治愈性疗法。越来越多的证据表明，在健康状态下，炎症消退是一个由特定化学介质精心编排的主动过程，这些介质被释放出来以恢复组织稳态。活化的细胞膜从磷脂中释放多不饱和脂肪酸，用于酶促转化为对固有免疫和适应性免疫具有深远调节作用的生物活性介质。其中一些介质具有抗炎和促消退作用，它们通过特定的识别位点以细胞类型特异性的方式进行转导，这些识别位点启动调节性细胞内信号，如前鲨烯二磷酸重塑，以限制促炎细胞的激活。在哮喘患者的气道中已鉴定出一些这些反调节脂质介质，其产生缺陷与疾病严重程度相关。在本综述中，我们描述了促消退化学介质的生物合成和生物作用，并提供了与哮喘特别相关的选定介质及其结构类似物的实例。
