Mineral dust promotes alterations in ferritin isoforms and oxidative damage to proteins in rat and human alveolar macrophages

James R. Connor, Brian Snyder, John L. Stauffer, Lesley J. Gaydos, Laurence M. Demers, Douglas C. Kuhn

Research output: Contribution to journalArticle

Abstract

The disposition of iron in the alveolar macrophage (AM) may be a critical factor in its reactivity to inhaled mineral dust. Dust particles such as coal and silica contain leachable iron or iron oxides on their surface which may become available as a catalyst for the generation of free radicals by the activated AM. This process may be regulated by iron storage proteins, which play an important role in the intracellular availability of iron. To characterize the relative effects of coal and silica dust on the content of the principal iron storage protein in the AM, we exposed human and rat AM to either respirable coal or silica dust (100 μg/ml) and evaluated the levels of intracellular ferritin. Analysis of ferritin isoforms (H- and L-chain) using monoclonal antibodies revealed a ratio of H- to L-isoforms of 1.6/1 in untreated human AM. Exposure of human AM to coal dust for 24 hours resulted in a 2.2-fold increase in the H-isoform and a 1.4-fold increase in the L-isoform. In contrast, silica dust exposure resulted in a 66 percent reduction in the levels of both ferritin isoforms. Analysis of total ferritin in rat AM using polyclonal antibody showed no change in ferritin levels on exposure to coal dust, but a 44 percent reduction in ferritin on exposure of AM to silica dust. Analyses of silica-induced oxidative protein modification through evaluation of protein carbonyl generation suggested a paradoxical relationship between alterations in ferritin isoforms and oxidative damage to total AM protein. In both human and rat AM, exposure of AM to silica resulted in a decrease in protein carbonyl generation. The results of these studies suggest that acute exposure to mineral dusts alters the levels of the major iron storage protein in the AM, and that this alteration is not associated with an increase in oxidative modification to total cellular protein.

Original languageEnglish (US)
Pages (from-to)969-972
Number of pages4
JournalApplied Occupational and Environmental Hygiene
Volume11
Issue number7
DOIs
StatePublished - Jul 1996

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health

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