Peptide targeting and imaging of damaged lung tissue in influenza-infected mice

Author: Li Na   Yin Lu   Thévenin Damien   Yamada Yoshiyuki   Limmon Gino   Chen Jianzhu   Chow Vincent TK   Engelman Donald M   Engelward Bevin P  

Publisher: Future Medicine

ISSN: 1746-0913

Source: Future Microbiology, Vol.8, Iss.2, 2013-02, pp. : 257-269

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Abstract

Aim: 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. Results: 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. Conclusion: 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.

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