Mw. Plautz et al., Influence of cigarette smoking on crocidolite-induced ferritin release by human alveolar macrophages, J LA CL MED, 136(6), 2000, pp. 449-456
Citations number
35
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Alveolar macrophages (AMs) mobilize iron from the surface of iron-containin
g minerals such as asbestos and synthesize ferritin for intracellular iron
storage or secretion. Although the synthesis of iron-free ferritin (apoferr
itin) provides antioxidant protection, the secretion of iron-containing fer
ritin 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. Th
e 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 cell
s in vitro. AMs recovered from nonsmokers (n = 8) or smokers (n = 8) were e
xposed to crocidolite or titanium dioxide (TiO2)(1 x 10(6) AMs, 50 to 200 m
ug/mL) for up to 18 hours. AMs exposed to crocidolite but not TiO2 showed i
ncreased cell content of iron and ferritin and increased cell supernatant f
erritin concentrations. Increases in iron and ferritin content were similar
for AMs recovered from smokers and those recovered from nonsmokers; howeve
r, 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 <mu>g/mL, 18 hours) caused dos
e-dependent cell death as indicated by lactate dehydrogenase release. The a
ddition of ferritin (greater than or equal to 500 mg/mL) but not apoferriti
n to culture media enhanced crocidolite-induced LDH release (P < .01). Thes
e findings suggest that cigarette smoking and crocidolite exposure have syn
ergistic effects that promote ferritin release by AMs, which could catalyze
oxidative injury to other alveolar cells.