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Am. J. Respir. Crit. Care Med., Volume 159, Number 1, January 1999, 100-106

Iron Uptake Promotes Hyperoxic Injury to Alveolar Macrophages

LEWIS J. WESSELIUS, WADE L. WILLIAMS, KIRSTIN BAILEY, SUSAN VAMOS, AMY R. O'BRIEN-LADNER, and THOMAS WIEGMANN

Department of Medicine, Kansas City Veterans Affairs Medical Center, Kansas City, Missouri; and Department of Medicine, University of Kansas School of Medicine, Kansas City, Kansas

Iron uptake by cells may increase the intracellular pool of prooxidant iron prior to storage of iron within ferritin. Because hyperoxia is toxic to alveolar macrophages (AM) via mechanisms involving oxidant stress, we hypothesized that iron uptake by AM might promote hyperoxia-induced injury. To assess this hypothesis, we cultured AM recovered from healthy volunteers under conditions of normoxia or hyperoxia (60% or 95% oxygen) in media of varying iron content, including control media (3 µM iron) and media supplemented with iron (FeCl3; total iron 10, 20, or 40 µM). AM injury was assessed by measuring release of lactate dehydrogenase (LDH), phagocytic activity for yeast, and cytosolic concentrations of calcium ([Ca2+]i) as determined by ratio image analysis of AM loaded with the fluorescent calcium probe indo-1. There was dose-dependent accumulation of iron and ferritin synthesis in AM exposed to iron-supplemented media. Exposure of AM to hyperoxia (60% and 95% oxygen, 18 h) in control media increased LDH release and impaired phagocytic activity for yeast; however, similar hyperoxic exposures in iron-supplemented media significantly increased the cells' LDH release and decreased phagocytosis. Exposure to 95% oxygen increased the [Ca2+]i of AM over 18 h, but similar exposure in iron-supplemented media induced greater increases in [Ca2+]i. As compared with exposure to normoxia, exposure to hyperoxia (60% and 95% oxygen) also decreased iron uptake and, to a greater extent, ferritin synthesis by AM in iron-supplemented media. These data suggest that: (1) iron uptake promotes hyperoxic injury to AM; and (2) hyperoxia impairs the capacity of AM to sequester iron in ferritin.




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Copyright © 1999 American Thoracic Society