The alveolar macrophage (AM) population has been shown to be heterogeneous in composition as well as in function. The aim of our study was to assess morphological and functional features of AM in an experimental model of quartz-induced lung fibrosis by flow cytometric methods. Twelve cynomolgus monkeys were exposed 8 hr/day, 5 days/week for 26 months to either normal atmosphere (n = 5) or 5 mg/m3 DQ12 < 5-mu-m quartz dust (n = 7). After 20 months of exposure, we studied AM phagocytosis by incubating bronchoalveolar lavage cells with fluorescent polystyrene microspheres (mean diameter 1.91-mu-m). Using a fluorescence-activated cell sorter analyzer, AM subpopulations were identified via their volume/side scatter properties. After selective electronic "gating" of the AM populations, both the percentage of phagocytic AM and the mean number of ingested microspheres per AM were determined. In addition, a phagocytic index (microspheres/AM x % phagocytic AM x 10(-2)) and a hypothetical total phagocytic capacity of one lung (phagocytic index x total number of AM x 10(-6)) were calculated. The total bronchoalveolar lavage cell counts rose (75.6 +/- 11.3 x 10(6) versus 10.1 +/- 0.8 x 10(6)) significantly after quartz exposure. In contrast, the percentage of phagocytic AM was significantly (p < 0.05) reduced (43.5 +/- 5.0% versus 74.2 +/- 1.4%). Flow cytometric measurements revealed the appearance of an AM subpopulation characterized by size/granularity features identical to blood monocytes. Only minimal numbers of these cells were found under normal conditions, but they constituted 50% of the entire AM population in the quartz group. Selective analysis of these AM subpopulations demonstrated a quartz-induced reduction of phagocytosis within the subpopulation of large AM (69.0 +/- 4.8% versus 85.8 +/- 4.9%), whereas the comparatively low phagocytic activity of smaller, monocytelike AM was slightly elevated (16.2 +/- 2. 1% versus 10.9 +/- 1.7%). High numbers of these relatively inactive cells led to a decreased phagocytic index (8.6 +/- 1.7 versus 16.2 +/- 2.3) that was, however, more than compensated for by the higher total AM numbers, leading to an enhanced pulmonary phagocytic capacity (403.6 +/- 85.2 versus 137.6 +/- 16.5). We conclude from these results that chronic quartz exposure causes a shift from large, active (with respect to phagocytosis) AM to small, monocytelike, less active AM. This effect is likely to be responsible for the relatively impaired phagocytic activity of the total AM population. Nevertheless, the total pulmonary phagocytic capacity is enhanced in quartz-exposed animals due to increased total AM numbers.
