PATTERNS OF PARTICLE DEPOSITION AND RETENTION AFTER INSTILLATION TO MOUSE LUNG DURING ACUTE INJURY AND FIBROTIC REPAIR

Studies an particle deposition, clearance, and translocation to the interstitium and lymph nodes have mostly been carried out on normal animals. This study evaluates changes in these parameters after inert particles are deposited in lungs during acute inflammatory injury and during fibrotic repair. Three days after instilling bleomycin to mouse lungs, there is an inflammatory response and necrosis of type 1 epithelium. When carbon is instilled in these lungs, particles appear uniformly distributed, some are engulfed by the increased phagocytes, but many particles cross the denuded epithelial surface to reach interstitial macrophages. Subsequently much carbon remains in the connective tissue and some reaches hilar lymph nodes. After 16 weeks, particle retention in the lung is significantly greater than in a carbon-only control group. Other mice received carbon 4 weeks after bleomycin when epithelial repair had occurred and many areas of the lung were fibrotic. Very little carbon reached these regions; most was deposited in less fibrotic areas of lung. Few particles crossed the epithelium so that retained carbon in lung and lymph nodes was equivalent to that in the carbon-only group. The results show that a fibrotic lung structure alters the patterns of particle deposition in the lung. However, the major factor determining enhanced particle retention is the integrity of the epithelium. Particle deposition at a time of epithelial injury is associated with enhanced translocation to interstitium and lymph nodes. This may result in pathologic changes if a normally nonreactive low dose of toxic particles is deposited when the epithelium is breached.