Arginase activity differs with allergen in the effector phase of ovalbumin- versus trimellitic anhydride-induced asthma

Amy L. Greene, Mark S. Rutherford, Ronald R. Regal, Gail H. Flickinger, Julie A. Hendrickson, Cecilia R Giulivi, Margaret E. Mohrman, Daniel G. Fraser, Jean F. Regal

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Both trimellitic anhydride (TMA), a small molecular weight chemical, and ovalbumin (OVA), a reference protein allergen, cause asthma with eosinophilia. To test the hypothesis that different allergens elicit symptoms of asthma via different effector pathways, gene expression was compared in lungs of Balb/c mice sensitized with either TMA or OVA, followed by intratracheal challenge with TMA conjugated to mouse serum albumin (TMA-MSA) or OVA, respectively. Sensitized animals challenged with mouse serum albumin (MSA) alone were controls. Seventy-two hours after challenge, lung eosinophil peroxidase indicated that both allergens caused the same significant change in eosinophilia. Total RNA was isolated from lung lobes of 6-8 animals in each of four treatment groups and hybridized to Affymetrix U74Av2 GeneChips. False discovery rates (q-values) were calculated from an overall F test to identify candidate genes with differences in expression for the four groups. Using a q-value cutoff of 0.1, 853 probe sets had significantly different expression across the four treatment groups. Of these 853 probe sets, 376 genes had an Experimental/Control ratio of greater than 1.2 or less than 1/1.2 for either OVA- or TMA-treated animals, and 249 of the 376 genes were uniquely up- or down-regulated for OVA or TMA (i.e., differentially expressed with the allergen). qRT-PCR analysis of selected transcripts confirmed the gene expression analysis. Increases in both arginase transcript and enzyme activity were significantly greater in OVA-induced asthma compared to TMA-induced asthma. These data suggest that pathways of arginine metabolism and the importance of nitric oxide may differ in OVA- and TMA-induced asthma.

Original languageEnglish (US)
Pages (from-to)420-433
Number of pages14
JournalToxicological Sciences
Volume88
Issue number2
DOIs
StatePublished - Dec 2005

Keywords

  • Allergy
  • Eosinophils
  • Lung
  • Nitric oxide
  • Rodent

ASJC Scopus subject areas

  • Toxicology

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    Greene, A. L., Rutherford, M. S., Regal, R. R., Flickinger, G. H., Hendrickson, J. A., Giulivi, C. R., Mohrman, M. E., Fraser, D. G., & Regal, J. F. (2005). Arginase activity differs with allergen in the effector phase of ovalbumin- versus trimellitic anhydride-induced asthma. Toxicological Sciences, 88(2), 420-433. https://doi.org/10.1093/toxsci/kfi311