Alterations of the arginine metabolome in asthma

Abigail Lara, Sumita B. Khatri, Zeneng Wang, Suzy A.A. Comhair, Weiling Xu, Raed A. Dweik, Melanie Bodine, Bruce S. Levison, Jeffrey Hammel, Eugene Bleecker, William Busse, William J. Calhoun, Mario Castro, Fan Chung Kian, Douglas Curran-Everett, Benjamin Gaston, Elliot Israel, Nizar Jarjour, Wendy Moore, Stephen P. PetersW. Gerald Teague, Sally Wenzel, Stanley L. Hazen, Serpil C. Erzurum

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

Rationale: As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation. Objectives: We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity. Methods: Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serumarginase activity. Inflammatory parameters, including fraction of exhaled NO (FENO), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated. Measurements and Main Results: Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of FENO and serum arginase activity. However, Arg bioavailability was positively associated with FE NO only in healthy control subjects; Arg bioavailability was unrelated to FENO or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma. Conclusions:Unlike FENO, Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.

Original languageEnglish (US)
Pages (from-to)673-681
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume178
Issue number7
DOIs
StatePublished - Oct 1 2008

Keywords

  • Arginase
  • Arginine
  • Asthma
  • Methylarginine
  • Nitric oxide

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Lara, A., Khatri, S. B., Wang, Z., Comhair, S. A. A., Xu, W., Dweik, R. A., Bodine, M., Levison, B. S., Hammel, J., Bleecker, E., Busse, W., Calhoun, W. J., Castro, M., Kian, F. C., Curran-Everett, D., Gaston, B., Israel, E., Jarjour, N., Moore, W., ... Erzurum, S. C. (2008). Alterations of the arginine metabolome in asthma. American Journal of Respiratory and Critical Care Medicine, 178(7), 673-681. https://doi.org/10.1164/rccm.200710-1542OC