Arginase activity differs with allergen in the effector phase of ovalbumin- versus trimellitic anhydride-induced asthma.
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.
Greene
Amy L
AL
Department of Biochemistry and Molecular Biology, Medical School Duluth, University of Minnesota, 55812, USA.
Rutherford
Mark S
MS
Regal
Ronald R
RR
Flickinger
Gail H
GH
Hendrickson
Julie A
JA
Giulivi
Cecilia
C
Mohrman
Margaret E
ME
Fraser
Daniel G
DG
Regal
Jean F
JF
D000485:Allergens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D001249:Asthma / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007442:Intubation, Intratracheal; D051379:Mice; D008807:Mice, Inbred BALB C; D046208:Microchip Analytical Procedures; D010047:Ovalbumin / Q000008:administration & dosage / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000485:Allergens; D010796:Phthalic Anhydrides; D012333:RNA, Messenger; C015559:trimellitic anhydride; D010047:Ovalbumin; D009195:Peroxidase; D001119:Arginase