Metabolomics in Lung Inflammation:A High-Resolution ¹H NMR Study of Mice Exposedto Silica Dust

ABSTRACT

Here we report the first ¹H NMR metabolomics studies on excised lungs and bronchoalveolar lavage fluid (BALF) from mice exposed to crystalline silica. High-resolution ¹H NMR metabolic profiling on intact excised lungs was performed using slow magic angle sample spinning (slow-MAS) ¹H PASS (phase-altered spinning sidebands) at a sample spinning rate of 80 Hz. Metabolic profiling on BALF was completed using fast magic angle spinning at 2 kHz. Major findings are that the relative concentrations of choline, phosphocholine (PC), and glycerophosphocholine (GPC) were statistically significantly increased in silica-exposed mice compared to sham controls, indicating an altered membrane choline phospholipids metabolism (MCPM). The relative concentrations of glycogen/glucose, lactate, and creatine were also statistically significantly increased in mice exposed to silica dust, suggesting that cellular energy pathways were affected by silica dust. Elevated levels of glycine, lysine, glutamate, proline, and 4-hydroxyproline were also increased in exposed mice, suggesting the activation of a collagen pathway. Furthermore, metabolic profiles in mice exposed to silica dust were found to be spatially heterogeneous, consistent with regional inflammation revealed by in vivo magnetic resonance imaging (MRI).

KEYWORDS :

• ¹H NMR
• MAS
• Metabolomics
• Metabolite
• Molecular Pathways
• MRI
• Inflammation