Source of iron in neutrophil-mediated killing of endothelial cells

Recently we have shown that human neutrophils activated with phorbol ester are cytotoxic for cultured bovine pulmonary artery endothelial cells in an iron-dependent manner. By using the ferric iron chelator deferoxamine mesylate, we have now investigated the source of the iron. Pretreatment of neutrophils with deferoxamine mesylate affected neither their production of O2- nor their cytotoxicity for endothelial cells after addition of phorbol ester. However, similar pretreatment of endothelial cells with deferoxamine mesylate, followed by washing of the cells, resulted in a persistent presence of chelator associated with the endothelial cells and high degrees of protection of endothelial cells from cytotoxicity. The protection was dependent on the amount of chelator used and on the duration of exposure of the endothelial cells to the chelator. These data suggest that iron, which plays an important role in oxygen radical-mediated killing of endothelial cells by neutrophils, is derived from the target (endothelial) cells.