title: Peptide targeting and imaging of damaged lung tissue in influenza-infected mice.
abstract: OBJECTIVE
  In this study, we investigate whether pH (low) insertion peptide (pHLIP) can target regions of lung injury associated with influenza infection.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Na
authors: N
authors: Li
authors: Lu
authors: L
authors: Yin
authors: Damien
authors: D
authors: Thévenin
authors: Yoshiyuki
authors: Y
authors: Yamada
authors: Gino
authors: G
authors: Limmon
authors: Jianzhu
authors: J
authors: Chen
authors: Vincent Tk
authors: VT
authors: Chow
authors: Donald M
authors: DM
authors: Engelman
authors: Bevin P
authors: BP
authors: Engelward
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005455:Fluorescent Antibody Technique; D006651:Histocytochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity; D007274:Injections, Intraperitoneal; D008168:Lung / Q000473:pathology* / Q000821:virology; D008565:Membrane Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology; D021381:Protein Transport
chemical_list: D008565:Membrane Proteins; C533201:pHLIP protein
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