Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity

作者：Dailey Lea Ann^*; Hernandez Prieto Raquel; Maria Casas Ferreira Ana; Jones Marie Christine; Riffo Vasquez Yanira; Rodriguez Gonzalo Encarnacion; Spina Domenico; Jones Stuart A; Smith Norman W; Forbes Ben; Page Clive; Legido Quigley Cristina

来源：Nanotoxicology, 2015, 9(1): 106-115.

DOI：10.3109/17435390.2014.894150

• AMP
• broncho-alveolar lavage
• hydrophobicity
• inflammation
• lung
• metabolomics
• nanoparticles

Inhaled nanomaterials present a challenge to traditional methods and understanding of respiratory toxicology. In this study, a non-targeted metabolomics approach was used to investigate relationships between nanoparticle hydrophobicity, inflammatory outcomes and the metabolic fingerprint in bronchoalveolar fluid. Measures of acute lung toxicity were assessed following single-dose intratracheal administration of nanoparticles with varying surface hydrophobicity (i.e. pegylated lipid nanocapsules, polyvinyl acetate nanoparticles and polystyrene beads; listed in order of increasing hydrophobicity). Broncho-alveolar lavage (BAL) fluid was collected from mice exposed to nanoparticles at a surface area dose of 220 cm(2) and metabolite fingerprints were acquired via ultra pressure liquid chromatography-mass spectrometry-based metabolomics. Particles with high surface hydrophobicity were proinflammatory. Multivariate analysis of the resultant small molecule fingerprints revealed clear discrimination between the vehicle control and polystyrene beads (p<0.05), as well as between nanoparticles of different surface hydrophobicity (p<0.0001). Further investigation of the metabolic fingerprints revealed that adenosine monophosphate (AMP) concentration in BAL correlated with neutrophilia (p<0.01), CXCL1 levels (p<0.05) and nanoparticle surface hydrophobicity (p<0.001). Our results suggest that extracellular AMP is an intermediary metabolite involved in adenine nucleotide-regulated neutrophilic inflammation as well as tissue damage, and could potentially be used to monitor nanoparticle-induced responses in the lung following pulmonary administration.

• 出版日期2015-2