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To investigate the possible mechanisms of the accumulation of particle-laden alveolar macrophages (AMs) in alveoli, male golden hamsters were exposed to coal fly ash (FA) at the concentration of 0 or 2 mg/m3 for 6 months (20 hr/day, 7 days/week) in the first series of experiments, and at 0, 1, 2, or 20 mg/m3 of FA for 3 months in the subsequent experiments. Particle-laden AMs accumulated dose- and time-dependently in alveoli. In the lungs of 1 and 2 mg/m3-exposed groups. AMs first appeared in a cluster in alveoli at the alveolar-bronchiole junctions proximal to the lobar bronchus. Agglomerated AMs in these regions were generally larger in size and ingested more particles than those in the peripheral regions. These results indicate that the accumulation of AMs is closely related to the amount of particles deposited in alveoli and that ingested by AMs. Histochemical analysis revealed that AMs with small amount of particles showed the positive activity of acid phosphatase. On the other hand, heavily particle-laden AMs showed no such activity. Scanning electron microscopic observations revealed the time-related formation of small blebs and loss of surface features on the cell surface of AMs. These results suggest that the accumulation of particle-laden AMs might be caused by the decrease and/or loss of their activities, especially their mobility during migration toward terminal bronchioles from alveoli, due to the increase of ingested particles in parallel with the prolongation of exposure time.

Accumulation of Alveolar Macrophages Induced by Inhalation Exposure of Coal Fly Ash in Golden Hamster Lungs