Iron binding, internalization, and fate in human alveolar macrophages.

Chronic inflammation in such diseases as rheumatoid arthritis has been associated with the accumulation of iron in mononuclear phagocytes. Cigarette smoking, which also produces chronic pulmonary inflammation, may be associated with iron accumulation in alveolar macrophages (AM). We have examined the total iron content in human AM and found it to be 43.0 +/- 7.7 (mean +/- SEM) and 12.8 +/- 1.3 nmol/1 X 10(6) cells (P less than 0.01) from smokers and nonsmokers, respectively. Because the higher iron content in smokers' macrophages may reflect increased internalization, the binding and uptake of iron-saturated transferrin was examined in cells from smokers and nonsmokers. However, no significant differences were found between the two groups. The smoking-related alteration in iron content may instead reflect differences in the fate of internalized iron. Iron internalized by AM as iron 59 initially bound to transferrin was distributed to a cytoplasmic, largely ferritin-associated, pool more slowly in smokers than in nonsmokers, during a 24-hour incubation in vitro. Significantly less newly internalized iron was returned to the culture medium by AM from smokers, which by 24 hours had released 11.0% +/- 3.7% of the initially internalized 59Fe compared with 36.0% +/- 2.3% for nonsmokers (P less than 0.01). The increased accumulation of iron by AM in the alveolar space of smokers may modulate hydroxyl radical production in the microenvironment of these cells.