Expression of xanthine oxidase activity by murine leukocytes.
The enzyme xanthine oxidase participates in the pathogenesis of tissue ischemia-reperfusion injury by depleting purine pools and generating toxic oxygen metabolites. The role of xanthine oxidase in inflammatory cell populations has not been defined. We examined the level of xanthine oxidase activity expressed by murine leukocytes both in the resting state, and after in vivo and in vitro exposure to inflammatory stimuli. The contribution of xanthine oxidase to inflammation may vary among tissue compartments, so leukocytes harvested from several tissues were studied. Resident murine peritoneal macrophages consistently expressed xanthine oxidase activity (291 +/- 55 microIU/10(6) cells). Thioglycolate-elicited peritoneal macrophages contained similar levels of xanthine oxidase activity (265 +/- 42 microIU/10(6) cells). By contrast, resident murine alveolar macrophages expressed one tenth the xanthine oxidase activity (24 +/- 4 microIU/10(6) cells). Xanthine oxidase activity was also consistently found in murine peritoneal neutrophils (127 +/- 28 microIU/10(6) cells) but not in splenic lymphocytes. In vitro studies were performed to determine whether xanthine oxidase activity of resident peritoneal macrophages could be modulated by exogenous stimuli relevant to the pathogenesis of inflammation. Lipopolysaccharide caused a 62% +/- 9% reduction in cellular xanthine oxidase activity (p less than 0.02). Interferon-gamma alone had no effect on xanthine oxidase activity; however, interferon-gamma and lipopolysaccharide together caused a striking reduction in cellular xanthine oxidase activity, reaching 25% +/- 2% of unstimulated control cells (p less than 0.001). We conclude that murine macrophages and neutrophils are potentially important sources of xanthine oxidase activity in inflamed tissues. In addition, the activity of xanthine oxidase in macrophages is tissue specific and is modulated in vitro by proinflammatory stimuli.
Grum
C M
CM
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360.
Gross
T J
TJ
Mody
C H
CH
Sitrin
R G
RG
D000818:Animals; D015870:Gene Expression; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010586:Phagocytes / Q000187:drug effects / Q000201:enzymology; D014969:Xanthine Oxidase / Q000235:genetics / Q000378:metabolism*
D008070:Lipopolysaccharides; D007371:Interferon-gamma; D014969:Xanthine Oxidase