Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance in Research & Technology, 1 CREATE Way, #03-12/13/14 Enterprise Wing, 138602, Singapore.
Future Microbiol. 2013 Feb;8(2):257-69. doi: 10.2217/fmb.12.134.
In this study, we investigate whether pH (low) insertion peptide (pHLIP) can target regions of lung injury associated with influenza infection.
MATERIALS & METHODS: Fluorophore-conjugated pHLIP was injected intraperitoneally into mice infected with a sublethal dose of H1N1 influenza and visualized histologically.
pHLIP specifically targeted inflamed lung tissues of infected mice in the later stages of disease and at sites where alveolar type I and type II cells were depleted. Regions of pHLIP-targeted lung tissue were devoid of peroxiredoxin 6, the lung-abundant antioxidant enzyme, and were deficient in pneumocytes. Interestingly, a pHLIP variant possessing mutations that render it insensitive to pH changes was also able to target damaged lung tissue.
pHLIP holds potential for delivering therapeutics for lung injury during influenza infection. Furthermore, there may be more than one mechanism that enables pHLIP variants to target inflamed lung tissue.
本研究旨在探讨低 pH 插入肽（pHLIP）是否可以靶向与流感感染相关的肺损伤区域。
将荧光标记的 pHLIP 经腹腔注射到感染低致死剂量 H1N1 流感的小鼠体内，并进行组织学观察。
pHLIP 特异性靶向感染后疾病晚期和肺泡 I 型和 II 型细胞耗竭的肺泡型细胞受损的肺部组织。pHLIP 靶向的肺部组织区域缺乏过氧化物酶 6，而过氧化物酶 6 是一种丰富存在于肺部的抗氧化酶，且其中的肺泡细胞缺失。有趣的是，一种对 pH 值变化不敏感的突变型 pHLIP 变体也能够靶向受损的肺部组织。
pHLIP 有可能成为流感感染期间肺部损伤治疗的载体。此外，可能存在一种以上的机制使 pHLIP 变体能够靶向炎症肺部组织。
