Differential expression of lung arginase and inos in sepsis

Published

Journal Article

The primary metabolic fates of L-arginine are conversion to L-citrulline by nitric oxide synthase(NOS) and conversion to L-ornithine by arginase. In the lung, the expression of the inducible form of NOS (iNOS) is enhanced in various states of inflammation, such as sepsis. The expression of arginase in the normal and septic lung, and its potential interrelationships with iNOS, however, are not known. We performed experiments to determine which of the two known isoforms of arginase is present in normal rat lung and to investigate its cellular distribution. Since arginase and iNOS share the same substrate, L-arginine, we also tested the hypothesis that the expression of arginase is related to iNOS expression in the lungs of septic rats. Lungs from six cecal ligation and puncture(CLP) and four sham-operated(S) rats ere harvested and homogenized after 16 hours. Western blot analyses were performed with polyclonal antibodies against two isoforms of rat arginase (I and II) and iNOS. Additional CLP and S lungs were obtained for parafin-fixation for immunohistochemistry with the same antibodies. We found arginase II to be the main isoform present in normal rat lung by Western blot at 39 kDa. Immunolocalization showed that arginase II is distributed primarily in alveolar epithelial cells, endothelial cells, alveolar macrophages, and Clara cells. After CLP, arginase II was no longer detectable in rat lungs at 16 hours. The iNOS was not detectable by Western blot or immunohistochemistry in normal Jung. After CLP, iNOS was strongly detectable in the lung at 16 hours. Immunohistochemistry showed heterogeneous iNOS distribution in macrophages and in alveolar epithelium. These data demonstrate constitutive expression of arginase II in normal rat lung which is lost as iNOS is upregulated during sepsis.

Duke Authors

Cited Authors

  • Carraway, MS; Piantadosi, CA; Jenkinson, CP; Huang, YC

Published Date

  • January 1, 1996

Published In

Volume / Issue

  • 44 / 3

International Standard Serial Number (ISSN)

  • 1708-8267

Citation Source

  • Scopus