Early Response of the Canine Respiratory Tract Following Long-Term Exposure to a Sulfur(IV) Aerosol at low Concentration. III. Macrophage-Mediated Long-Term Particle Clearance

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Abstract
After a control period of 400 d in filtered, contaminant-free air, eight dogs were exposed continuously for 290 d to a respirable sulfur(IV) aerosol at an S(IV) concentration of 0.3mg−3, equivalent to a sulfur dioxide concentration of 0.6 mg m−3. Long-term particle clearance from the lungs was tested with uniform, moderately soluble cobalt oxide (Co3O4)particles and nearly insoluble fused aluminosilicate particles (FAP) after short-term inhalation. The former were used to analyze translocation of dissolved particle mass from the lungs to blood, and the latter to study mechanical particle transport from the lungs to the larynx and into the gastrointestinal tract, and via lymphatics to the lung-associated lymph nodes. The in vivo translocation rate of moderately soluble test particles was significantly increased (by a factor of 7.8) in three dogs during S(IV) exposure compared to the rate during the control period. The results were confirmed by in vitro measurements of intracellular dissolution of moderately soluble Co3O4 particles in alveolar macro-phages obtained from serial bronchoalveolar lavages of the dogs. Moreover, the in vitro studies showed a significant increase on average in intracellular particle dissolution in macrophages (by a factor of 1.3) from 2 mo until the end of exposure, indicating changes in alveolar macrophage function leading to enhanced particle clearance by translocation. Long-term mechanical particle transport (MPT) from the lungs to the larynx was a very slow clearance mechanism in the dogs, starting with a rate of 0.002 day−1 of the retained particles, which decreased exponentially. Thus the nearly insoluble FAP were in fact more effectively cleared by translocation than by MPT In five dogs, MPT during exposure was more effective by a factor of five than expected from the MPT during the control period. In contrast, MPT in two dogs was reduced by a factor of 0.3. The mechanical particle transport to the lung-associated lymph nodes during the entire period of the study showed a substantial intersubject variability of between 0.02 and 0.13 of the long-term retained FAP. The results indicate early changes in long-term particle clearance in the lungs following continuous exposure to S(IV). Since both clearance mechanisms are alveolar macrophage mediated, the alterations indicate the presence of functional changes in the phagolysosomal vacuole and in factors affecting the motility of alveolar macrophages on the epithelial surface.