INCREASED RELEASE OF FERRITIN AND IRON BY IRON-LOADED ALVEOLAR MACROPHAGES IN CIGARETTE SMOKERS

The lower respiratory tract of cigarette smokers contains an increased amount of iron that is predominantly sequestered within alveolar macr ophages (AM), but is also present in alveolar epithelial fluid. Extrac ellular ferritin-bound iron could potentially be released by reductant s present in cigarette smoke and catalyze generation of highly reactiv e hydroxyl radicals capable of causing oxidant injury. To determine wh ether AM are a source of alveolar extracellular ferritin and iron, we assessed in vitro release of iron, ferritin, and transferrin by AM rec overed by bronchoalveolar lavage (BAL) of 27 healthy subjects includin g nine nonsmokers (NS), nine light smokers (LS), and nine heavy smoker s (HS). Release of iron in vitro over 20 h was increased in AM recover ed from LS (2.24 +/- 0.21 nmol/10(6) AM/20 h, p < 0.001) and HS (3.11 +/- 0.32 nmol/10(6) AM, p < 0.001) compared with NS (1.28 +/- 0.08 nmo l/10(6) AM). Release of ferritin in vitro over 20 h was also increased in AM recovered from LS (71 +/- 24 ng/10(6) AM, p < 0.05) and HS (176 +/- 35 ng/10(6), p < 0.001) compared with NS (18 +/- 3 ng/10(6) AM). AM recovered from 12 smokers (8 HS, 4 LS) contained greater than 10 nm ol of iron per 10(6) cells. These iron-loaded AM released a greater pe rcentage of cell ferritin stores in vitro over 4 h (8.4% +/- 1.1, p < 0.01) than did AM from NS (3.2% +/- 0.6). Release of lactate dehydroge nase (LDH) over 4 h was substantially less (2.9% +/- 0.3, p < 0.001) t han ferritin release. Ferritin release by AM in vitro over 20 h correl ated with concentrations of ferritin present in BAL fluid (r = 0.80, p < 0.001) for all subjects. Transferrin release in vitro by AM from ea ch group was similar. These data suggest that high concentrations of e xtracellular ferritin and iron in alveolar structures of some cigarett e smokers may be derived, in part, from release of ferritin and iron b y iron-loaded AM.