Ali Md Khadem, Kim Richard Y, Karim Rafia, Mayall Jemma R, Martin Kristy L, Shahandeh Ali, Abbasian Firouz, Starkey Malcolm R, Loustaud-Ratti Veronique, Johnstone Daniel, Milward Elizabeth A, Hansbro Philip M, Horvat Jay C
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan NSW 2308, Australia.
Global Centre for Environmental Remediation, Faculty of Science, the University of Newcastle, Callaghan, NSW 2308, Australia.
Int J Biochem Cell Biol. 2017 Jul;88:181-195. doi: 10.1016/j.biocel.2017.05.003. Epub 2017 May 7.
Iron is essential for many biological processes, however, too much or too little iron can result in a wide variety of pathological consequences, depending on the organ system, tissue or cell type affected. In order to reduce pathogenesis, iron levels are tightly controlled in throughout the body by regulatory systems that control iron absorption, systemic transport and cellular uptake and storage. Altered iron levels and/or dysregulated homeostasis have been associated with several lung diseases, including chronic obstructive pulmonary disease, lung cancer, cystic fibrosis, idiopathic pulmonary fibrosis and asthma. However, the mechanisms that underpin these associations and whether iron plays a key role in the pathogenesis of lung disease are yet to be fully elucidated. Furthermore, in order to survive and replicate, pathogenic micro-organisms have evolved strategies to source host iron, including freeing iron from cells and proteins that store and transport iron. To counter these microbial strategies, mammals have evolved immune-mediated defence mechanisms that reduce iron availability to pathogens. This interplay between iron, infection and immunity has important ramifications for the pathogenesis and management of human respiratory infections and diseases. An increased understanding of the role that iron plays in the pathogenesis of lung disease and respiratory infections may help inform novel therapeutic strategies. Here we review the clinical and experimental evidence that highlights the potential importance of iron in respiratory diseases and infections.
铁对许多生物过程至关重要，然而，铁过多或过少都会导致各种各样的病理后果，这取决于受影响的器官系统、组织或细胞类型。为了减少发病机制，全身的铁水平通过控制铁吸收、全身运输以及细胞摄取和储存的调节系统受到严格控制。铁水平改变和/或体内稳态失调与多种肺部疾病有关，包括慢性阻塞性肺疾病、肺癌、囊性纤维化、特发性肺纤维化和哮喘。然而，这些关联背后的机制以及铁是否在肺部疾病发病机制中起关键作用尚未完全阐明。此外，为了生存和繁殖，致病微生物已经进化出获取宿主铁的策略，包括从储存和运输铁的细胞和蛋白质中释放铁。为了对抗这些微生物策略，哺乳动物进化出了免疫介导的防御机制，以减少病原体可利用的铁。铁、感染和免疫之间的这种相互作用对人类呼吸道感染和疾病的发病机制及管理具有重要影响。对铁在肺部疾病和呼吸道感染发病机制中所起作用的进一步了解可能有助于制定新的治疗策略。在此，我们综述了突出铁在呼吸道疾病和感染中潜在重要性的临床和实验证据。
