Alveolar macrophages accumulate iron and ferritin after in vivo exposure to iron or tungsten dusts

Abstract

Extracellular iron present in alveolar structures may contribute to oxidative lung injury induced by toxic mineral dusts by enhancing dust-induced generation of hydroxyl radicals. Alveolar macrophages (AMs) can sequester iron within ferritin and limit generation of hydroxyl radicals. In the current study we sought to assess whether AMs accumulate iron and ferritin after in vivo exposure to a dust with high iron content, to iron oxide, or to an inflammatory dust, calcium tungstate. We performed lung lavage 1, 7, 14, 28, 42, and 56 days after intracheal instillation of mineral dust in saline solution or instillation of saline solution alone and quantitated cell recovery and AM content of iron and ferritin. Instillation of iron oxide increased neutrophil recovery only on day 1 when compared with results in controls, whereas calcium tungstate increased neutrophil recovery through day 14. AMs recovered after instillation of iron oxide contained increased amounts of iron and ferritin, beginning on day 1 and progressing through day 56 after treatment (7.57 ± 0.38 μg iron per 10 6 AMs vs 1.54 ± 0.28 μg iron per 10 6 AMs for controls, p < 0.001; and 5908 ± 768 ng ferritin per 10 6 AMs vs 395 ± 20 ng ferritin per 10 6 AMs, p < 0.001). AMs recovered after calcium tungstate instillation also contained increased amounts of iron and ferritin beginning 14 days after treatment, with greatest content 42 days after treatment (4.85 ± 0.68 μg iron per 10 6 AMs, p < 0.001, and 2274 ± 736 ng ferritin per 10 6 AMs, p < 0.001). Tumor necrosis factor, which can enhance iron accumulation by macrophages, was spontaneously released by AMs recovered from tungsten-treated rats. These studies indicate that AMs accumulate iron and ferritin in response to both iron loading of the lungs with iron oxide exposure and lung inflammation induced by calcium tungstate exposure.