ENDOTHELIAL-CELL INJURY CAUSED BY CANDIDA-ALBICANS IS DEPENDENT ON IRON

Although it is known that Candida albicans causes endothelial cell inj ury, in vitro and in vivo, the mechanism by which this process occurs remains unknown. Iron is critical for the induction of injury in many types of host cells, Therefore, we investigated the role of iron in Ca ndida-induced endothelial cell injury. We found that pretreatment of e ndothelial cells with the iron chelators phenanthroline and deferoxami ne protected them from candidal injury, even though the organisms germ inated and grew normally, Loading endothelial cells with iron reversed the cytoprotective effects of iron chelation, Moreover, chelation of endothelial cell iron significantly reduced phagocytosis of C. albican s by these cells, while candidal adherence to chelator-treated endothe lial cells was slightly enhanced, Since endothelial cell phagocytosis of C. albicans is required for endothelial cell injury to occur, inhib ition of phagocytosis is likely the principal mechanism of the cytopro tective effects of iron chelation, The production of toxic reactive ox ygen intermediates by host cells is known to be inhibited by iron chel ation, Therefore, we investigated whether treating endothelial cells w ith antioxidants could mimic the cytoprotective effects of iron chelat ion, Neither extracellular nor membrane-permeative antioxidants reduce d candidal injury of endothelial cells. Furthermore, depleting endothe lial cells of the endogenous antioxidant glutathione did not render th em more susceptible to damage by C. albicans, These results suggest th at candida! injury of endothelial cells is independent of the producti on of reactive oxygen intermediates and that the cytoprotective effect s of iron chelation are not due to inhibition of the synthesis of thes e toxic intermediates.