Alveolar Macrophage Mediated Pulmonary Clearance Suppressed by Drug-Induced Phospholipidosis

Drug-induced phospholipidosis in rats treated with chlorphentermine (CP) for 4-7 days suppressed totally alveolar pulmonary clearance in the first days after a TiO2 aerosol exposure. Reversing phospholipidosis by treatment interruption led to a recovery of particle clearance. Morphological observations indicated that "foam cells" contained less TiO2 particles than alveolar macrophages (AM) of control rats. Clearance of ZnO particles which seems not to be mediated by AM was not affected by CP treatment. A grand average retention curve based on data from control groups of past experiments suggests that alveolar clearance of TiO2 particles has a phase 1 (T 1/2 = 7 days) lasting about 2 weeks and a phase 2 (T 1/2 = 69 days). The results with drug-induced phospholipidosis suggest that phase 1 is practically totally AM-mediated. Drug-induced phospholipidosis is a promising method for the study of AM involvement in defensive functions.