Ascorbic acid content and accumulation by alveolar macrophages from cigarette smokers and nonsmokers

The lung is at risk for injury from inhaled oxidants, including components of cigarette smoke; therefore, maintaining a chemical antioxidant defense would be advantageous. The potential for ascorbic acid to assume this protective role was investigated by comparing the total ascorbate content of alveolar macrophages obtained from human smokers and nonsmokers, from hamsters that were exposed to cigarette smoke for 4 to 6 weeks, and from a control group of unexposed hamsters. The abilities of alveolar macrophages from these four sources to accumulate ¹⁴C-labeled ascorbic acid and dehydroascorbate were also compared. The total ascorbate content in hamster macrophages was 19.5 ± 1.7 and 44.3 ± 2.8 nmol/10⁷ cells for nonsmokers and smokers, respectively (mean ± SEM, n = 4, p < 0.01), and in human macrophages was 31.3 ± 4.5 (n = 5) and 73.8 ± 13.1 nmol/10⁷ cells (n = 13, p < 0.1) for nonsmokers and smokers, respectively. In both humans and hamsters, the rates of accumulation of ascorbic acid and dehydroascorbate were significantly greater (p < 0.05) for alveolar macrophages from smokers compared with nonsmokers of the same species. After internalization, ≥70% of the dehydroascorbate was reduced to ascorbic acid by alveolar macrophages from nonsmokers and smokers of both species. An aqueous extract of cigarette smoke oxidized significantly more ascorbic acid to dehydroascorbate in vitro than a comparable volume of phosphate-buffered saline solution without smoke. The increased content of total ascorbate in alveolar macrophages from smokers and their enhanced ability to accumulate ascorbic acid and dehydroascorbate in vitro may reflect protective utilization of ascorbic acid under conditions of increased oxidant stress, compared with nonsmokers. In addition, alveolar macrophages may internalize dehydroascorbate that has been generated by oxidants in the alveolar space and reduce it to ascorbic acid so it can be reused as an antioxidant.