The study investigates the protective role of ferritin in endothelial cells against oxidant damage. Phagocyte-mediated oxidant damage to vascular endothelium is implicated in various vasculopathies, including atherosclerosis and pulmonary leak syndromes. The researchers found that heme, a hydrophobic iron chelate, rapidly accumulates in endothelial cells and exacerbates cytotoxicity caused by oxidants. However, when endothelial cells are briefly pulsed with heme and then incubated for a prolonged period (16 hours), they become highly resistant to oxidant-mediated injury. This protection is associated with the induction of heme oxygenase and ferritin mRNA within 4 hours. After 16 hours, heme oxygenase and ferritin levels increase approximately 50-fold and 10-fold, respectively. Ferritin, rather than heme oxygenase, is identified as the primary cytoprotective agent. Ferritin inhibits oxidant-mediated cytolysis in a dose-responsive manner and is effective even when added exogenously to cultured endothelial cells. The protective effect of ferritin is attributed to its ability to sequester intracellular iron and its ferroxidase activity, which prevents the accumulation of free iron that can cause oxidative damage. The study suggests that ferritin may play a crucial role in protecting endothelial cells from oxidant damage, potentially contributing to the development of therapeutic strategies for vasculopathies.The study investigates the protective role of ferritin in endothelial cells against oxidant damage. Phagocyte-mediated oxidant damage to vascular endothelium is implicated in various vasculopathies, including atherosclerosis and pulmonary leak syndromes. The researchers found that heme, a hydrophobic iron chelate, rapidly accumulates in endothelial cells and exacerbates cytotoxicity caused by oxidants. However, when endothelial cells are briefly pulsed with heme and then incubated for a prolonged period (16 hours), they become highly resistant to oxidant-mediated injury. This protection is associated with the induction of heme oxygenase and ferritin mRNA within 4 hours. After 16 hours, heme oxygenase and ferritin levels increase approximately 50-fold and 10-fold, respectively. Ferritin, rather than heme oxygenase, is identified as the primary cytoprotective agent. Ferritin inhibits oxidant-mediated cytolysis in a dose-responsive manner and is effective even when added exogenously to cultured endothelial cells. The protective effect of ferritin is attributed to its ability to sequester intracellular iron and its ferroxidase activity, which prevents the accumulation of free iron that can cause oxidative damage. The study suggests that ferritin may play a crucial role in protecting endothelial cells from oxidant damage, potentially contributing to the development of therapeutic strategies for vasculopathies.