Differential sensitivity of human fibroblasts and endothelial cells to reactive oxygen metabolites

Reactive oxygen metabolites are implicated in tissue damage, which is often followed by fibrosis. Our aim was to evaluate the sensitivity of human fibroblasts, in comparison with umbilical vein endothelial cells, to two common reactive oxygen metabolites, to superoxide produced by hypoxanthine and xanthine oxidase, and to reagent hydrogen peroxide. Depletion of the prelabeled adenine nucleotide pool, which is a sensitive index of cell damage, was used as the basis for comparison. In the presence of hypoxanthine, xanthine oxidase caused a dose-dependent nucleotide depletion, which was more pronounced in endothelial cells. After 4 h of exposure to 100 microM hypoxanthine and 80 mU/mL xanthine oxidase, fibroblasts retained 73 +/- 2% of their adenine nucleotides but endothelial cells retained only 11 +/- 2%. Hydrogen peroxide also had a larger effect on endothelial cells; after exposure to 100 microM for 30 min, adenine nucleotides retained 36 +/- 26% of their initial radioactivity in endothelial cells but 76 +/- 8% in fibroblasts. We conclude that umbilical vein endothelial cells are inherently more sensitive to the harmful effects of reactive oxygen metabolites than are fetal skin fibroblasts.