American Review of Respiratory Disease

Alveolar macrophages (AM) contain iron and ferritin, and concentrations of both are increased in AM of smokers compared with nonsmokers. Ferritin stores iron in a nontoxic form but can release iron in the presence of reducing agents and thereby catalyze the generation of toxic hydroxyl radicals via the Haber-Weiss reaction. Two distinct isoferritins are found in peripheral monocytes, L ferritin and H ferritin. H ferritin is the predominant isoferritin in human monocytes and is more effective than L ferritin in detoxifying iron in vitro. In this study we quantitated content of H and L ferritins, transferrin, and iron in AM recovered by bronchoalveolar lavage (BAL) of 24 subjects, including eight nonsmokers, eight smokers with normal spirometry, and eight smokers with chronic airflow obstruction (CAO). Of total AM ferritin in nonsmokers 95% was composed of L ferritin. Smokers without CAO demonstrated a 6.5-fold increase in the AM content of L ferritin (1,886 ± 266 versus 290 ± 51 ng, mean ± SEM; p < 0.0001) and a 3.8-fold increase in H ferritin (61 ± 18 versus 16 ± 2 ng per 1 × 106 AM, p < 0.01) compared with nonsmokers. Compared with smokers without CAO, AM recovered from smokers with CAO demonstrated a greater increase in L ferritin (5,059 ± 493 versus 1,886 ± 266 ng per 1 × 106 AM, p < 0.002) but a similar increase in H ferritin (64 ± 8 versus 61 ± 18 per 1 × 106 AM). The iron content of AM was also significantly greater in smokers with CAO compared with smokers without CAO (1,384 ± 235 versus 610 ± 123 ng per 1 × 106 AM, p < 0.01). The transferrin contents of AM recovered from nonsmokers, smokers without CAO, and smokers with CAO were similar (418 ± 56, 584 ± 171, and 396 ± 121 ng per 1 × 106, respectively). The data suggest that smokers with CAO have a greater accumulation of iron in AM than smokers without CAO. The increase in AM iron in both groups of smokers is associated with a marked increase in AM ferritin content, which is comprised predominantly of L-type ferritin.


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