Metabolic spectroscopy of inflammation in a bleomycin-induced lung injury model using hyperpolarized 1-13C pyruvate

Hoora Shaghaghi, Stephen Kadlecek, Charuhas Deshpande, Sarmad Siddiqui, Daniel Martinez, Mehrdad Pourfathi, Hooman Hamedani, Masaru Ishii, Harrilla Profka, Rahim Rizi

Research output: Contribution to journalArticle

Abstract

Metabolic activity in the lung is known to change in response to external insults, inflammation, and cancer. We report measurements of metabolism in the isolated, perfused rat lung of healthy controls and in diseased lungs undergoing acute inflammation using hyperpolarized 1-13C-labeled pyruvate. The overall apparent activity of lactate dehydrogenase is shown to increase significantly (on average by a factor of 3.3) at the 7 day acute stage and to revert substantially to baseline at 21 days, while other markers indicating monocarboxylate uptake and transamination rate are unchanged. Elevated lung lactate signal levels correlate well with phosphodiester levels as determined with 31P spectroscopy and with the presence of neutrophils as determined by histology, consistent with a relationship between intracellular lactate pool labeling and the density and type of inflammatory cells present. We discuss several alternate hypotheses, and conclude that the most probable source of the observed signal increase is direct uptake and metabolism of pyruvate by inflammatory cells and primarily neutrophils. This signal is seen in high contrast to the low baseline activity of the lung.

Original languageEnglish (US)
Pages (from-to)939-947
Number of pages9
JournalNMR in biomedicine
Volume27
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • Hyperpolarized
  • Inflammation
  • Lung
  • Macrophage
  • Metabolism
  • Neutrophil

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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    Shaghaghi, H., Kadlecek, S., Deshpande, C., Siddiqui, S., Martinez, D., Pourfathi, M., Hamedani, H., Ishii, M., Profka, H., & Rizi, R. (2014). Metabolic spectroscopy of inflammation in a bleomycin-induced lung injury model using hyperpolarized 1-13C pyruvate. NMR in biomedicine, 27(8), 939-947. https://doi.org/10.1002/nbm.3139