Role of the alveolar macrophage in the induction of pulmonary phospholipidosis by chlorphentermine. I. Drug and phospholipid levels.

In this study we have shown that the alveolar macrophage (AM) plays a major role in the induction of phospholipidosis in rat lung by chlorphentermine (CP). Rats were administered CP (30 mg/kg i.p., 5 days/week) for 1, 4 and 8 weeks and the levels of CP and total phospholipid were measured in whole lungs and in the AM fraction recovered from the lungs by pulmonary lavage. Lungs accumulate CP to a much greater extent than liver or kidney and show a marked increase in phospholipid content by 8 weeks. Drug treatment is accompanied by the recovery of an elevated number of AMs at all time points. The CP and phospholipid levels in AMs reach a peak at 4 weeks with little change beyond that time. Initially the phospholipidosis is localized largely in the AMs with the disorder developing in other compartments of the lungs with increasing treatment time. The AMs contribute 3% of the total pulmonary phospholipid in control rats. After 1 week of CP, 34% of the pulmonary phospholipid is in the AM fraction with this value being 21% after 8 weeks. The CP to phospholipid molar ratio is higher in AMs than whole lung at all three time points.