TY - JOUR T1 -支气管扩张症中性粒细胞功能障碍:J DO - 10.1183/13993003.03157-2020 SP - 2003157 AU - Giam, Yan Hui AU - Shoemark, Amelia AU - ChalmersJames D Y1 - 2011/01/01 UR - //www.qdcxjkg.com/content/early/2021/01/21/13993003.03157-2020.abstract N2 -支气管扩张是一种异质性疾病，有多种潜在原因。其病理生理学尚不清楚，但嗜中性粒细胞炎症和致病菌的功能失调被认为是关键。然而，目前尚无针对支气管扩张症的直接针对中性粒细胞炎症的许可治疗方法。在这篇综述中，我们讨论了我们目前对中性粒细胞功能障碍和支气管扩张的治疗靶向的理解。免疫代谢重编程是一种炎症通过改变细胞内代谢途径改变炎症细胞行为的过程，在多种炎症和自身免疫疾病中日益被认识到。在这里，我们展示了证据，在支气管扩张中观察到的中性粒细胞功能障碍与免疫代谢重编程是一致的。以往针对中性粒细胞的治疗尝试主要集中在减少中性粒细胞数量，从而增加感染。需要新的方法，我们提出，靶向代谢可以在理论上逆转中性粒细胞功能障碍和炎症失调。 As an exemplar, AMPK activation has already been shown to reverse phagocytic dysfunction and neutrophil extracellular trap formation in models of pulmonary disease. AMPK modulates multiple metabolic pathways including glycolysis which is critical for energy generation in neutrophils. AMPK activators can reverse metabolic reprogramming and are already in clinical use and/or development. We propose the need for a new immunomodulatory, rather than anti-inflammatory, approach to enhance bacterial clearance and reduce bronchiectasis disease severity.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Giam has nothing to disclose.Conflict of interest: Dr. Shoemark has nothing to disclose.Conflict of interest: Dr. Chalmers reports grants and personal fees from Astrazeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Chiesi, grants and personal fees from Glaxosmithkline, grants from Gilead Sciences, grants and personal fees from Insmed, personal fees from Novartis, personal fees from Zambon, outside the submitted work;. ER -