Cellular Responses and Translocation of Particles Following Deposition in the Lung

Publisher Website
Google Scholar
Abstract
Instillation of carbon into mouse lung results in a rapid increase in cells recovered by bronchoalveolar lavage. Initially the increase is due to polymorphonuclear leukocytes (PMN), then after 12 hours, alveolar macrophage (AM) numbers increase and reach a maximum at 2-3 days. Whereas the initial increase in AM is due to migration of monocyte-derived cells, after 1 day AM numbers are maintained by proliferation and migration of interstitial cell precursors. In a particle overload situation, the number of AM recovered at 1 day peaked with a 1.0 mg dose and did not increase as the dose was raised though the duration of the maximal response was extended. At high levels, translocation of particles into lung parenchyma was seen and carbon was found in Type 1 epithelial cells, in interstitial macrophages (IM) and in hilar lymph nodes. An alveolar overload situation was induced by reducing phagocytosis and clearance. We instilled carbon to the lungs of mice depleted of leukocytes by whole body irradiation. The usual eflux of PMN and AM was delayed and reduced, leading to greater particle transfer to the interstitium and lymph nodes than after carbon alone. When silica was injected to irradiated mice, the increase in PMN and AM was reduced, and many particles reached the IM. At 16 weeks radiated mice that received silica had a higher weight of retained particles in the lungs, and collagen measurements were much higher than after silica or irradiation alone. The results suggest that alveolar overload greatly enhances particle translocation to the interstitium where secretion of any macrophage-derived factors is more likely to be effective in fibroblast stimulation.