Influence of cigarette smoking on crocidolite-induced ferritin release by human alveolar macrophages.
Alveolar macrophages (AMs) mobilize iron from the surface of iron-containing minerals such as asbestos and synthesize ferritin for intracellular iron storage or secretion. Although the synthesis of iron-free ferritin (apoferritin) provides antioxidant protection, the secretion of iron-containing ferritin by AMs could increase the availability of catalytic iron in the lungs. Cigarette smoking may promote the secretion of ferritin by AMs after iron acquisition from mineral sources, because smokers' AMs are iron loaded. The first objective of this study was to determine whether ferritin secretion/release by AMs after in vitro exposure to crocidolite asbestos is enhanced by cigarette smoking. The second objective was to assess whether exogenous ferritin-bound iron could enhance the toxicity of crocidolite to lung cells in vitro. AMs recovered from nonsmokers (n = 8) or smokers (n = 8) were exposed to crocidolite or titanium dioxide (TiO2)(1 x 10(6) AMs, 50 to 200 microg/mL) for up to 18 hours. AMs exposed to crocidolite but not TiO2 showed increased cell content of iron and ferritin and increased cell supernatant ferritin concentrations. Increases in iron and ferritin content were similar for AMs recovered from smokers and those recovered from nonsmokers; however, increases in supernatant ferritin were >7-fold greater for smokers' AMs than for nonsmokers' AMs (P < .001). Exposure of A549 cells, a lung cancer-derived cell line, to crocidolite (50 to 200 microg/mL, 18 hours) caused dose-dependent cell death as indicated by lactate dehydrogenase release. The addition of ferritin (> or = 500 mg/mL) but not apoferritin to culture media enhanced crocidolite-induced LDH release (P < .01). These findings suggest that cigarette smoking and crocidolite exposure have synergistic effects that promote ferritin release by AMs, which could catalyze oxidative injury to other alveolar cells.
Plautz
M W
MW
Pulmonary Medicine Section, Carl T. Hayden Veterans Affairs Medical Center, Phoenix, Arizona 85012, USA.
Bailey
K
K
Wesselius
L J
LJ
D000328:Adult; D001052:Apoferritins / Q000378:metabolism; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D016022:Case-Control Studies; D002460:Cell Line; D005293:Ferritins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects* / Q000503:physiopathology*
D017638:Asbestos, Crocidolite; D005293:Ferritins; D001052:Apoferritins; D007501:Iron; D007770:L-Lactate Dehydrogenase