Xanthine oxidoreductase is an important cytoplasmic source of reactive oxyg
en species, and has been implicated in the pathogenesis of ischemia-reperfu
sion damage. Because the cellular localization of this protein remains uncl
ear, our aim was to study its distribution in fresh normal human tissue obt
ained at surgery. For immunohistochemical studies we purified the protein f
rom human milk and raised a polyclonal antibody in rabbits. In the liver th
e protein was preferentially localized to the periportal hepatocytes and it
was absent from the perivenous region. In the proximal intestine, the prot
ein was expressed in epithelial cells and goblet cells. Lactating mammary g
land acinar cells showed intense staining. Small vessel vascular endothelia
l cells of the intestine, mammary gland, and skeletal muscle showed immunor
eactivity, but in the kidney, glomerular endothelial cells were negative. N
o cells in the heart, brain, or lung expressed the enzyme protein. The obse
rved localization of the xanthine oxidoreductase protein is consistent with
previously observed enzyme activities in the organs studied. The widely as
sumed exclusive localization to capillary endothelium obviously does not ap
ply to humans.