Pulmonary inflammation and fibrosis following subacute inhalational exposure to silica: determinants of progression.
To evaluate components of the pulmonary cellular response to inhaled silica that might be determinants of progression to fibrosis, we developed a model of the early stages of chronic human silicosis. Groups of mice were subacutely exposed either to alpha-quartz or to nonfibrogenic titanium dioxide dust as a control. Induction of lesions by inhaled silica was dependent upon the size distribution and dose of the particles. A novel observation was that low intensity exposure to silica evoked reversible inflammatory lesions that were characterized by focal aggregation of particle-laden alveolar macrophages near terminal airways. In contrast, higher intensity exposure elicited progressive pulmonary inflammation, including a significant perivascular influx of T-lymphocytes early in the response. The airspace inflammatory lesions exhibited a statistically significant decline in numerical density over time. Meanwhile, deposition of collagen was observed at perivascular locations, which were anatomically distinct from the initial foci of inflammation, and the numerical density of fibrotic lesions increased significantly with time. We speculate that this pattern of response might be related to alveolar clearance mechanisms being overwhelmed, followed by translocation and sequestration of particles in the interstitium, subsequently leading to T-lymphocyte recruitment and ultimately to the development of fibrosis.
Velan
G M
GM
School of Pathology, University of New South Wales, Sydney.
Kumar
R K
RK
Cohen
D D
DD
D000210:Acute-Phase Reaction / Q000209:etiology / Q000473:pathology*; D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000009:adverse effects*; D012829:Silicosis / Q000473:pathology*; D013997:Time Factors
D012822:Silicon Dioxide