Foam cell formation of alveolar macrophages in Clara cell ablated mice inhaling crystalline silica.

We investigated the function of Clara cells in vivo during exposure to inhaled crystalline silica by morphological and immunohistochemical examination of intra-alveolar cells and alveolar macrophages in Clara cell-ablated mice. The Clara cells of male FVB/n mice (8-12 weeks old) were ablated by intraperitoneal administration of naphthalene (300 mg/kg). The mice were then exposed to crystalline silica (Min-U-Sil-5, 97.1 ± 9.5 mg/m³, 6 hours/day, 5 days/week) for up to two weeks. The lungs were assessed by morphometry, as well as by immunohistochemistry of CD36, lectin-like oxygenated low-density lipoprotein receptor (LOX)-1, and matrix metalloproteinases (MMPs) -2, -9 and -12. There was a significantly greater number of intra-alveolar cells in Clara cell-ablated mouse groups than in wild-type mouse groups that were exposed to crystalline silica. A marked number of foamy alveolar macrophages were only detected in the Clara cell-ablated group exposed to crystalline silica, indicating that Clara cells inhibit infiltration and foam cell formation of alveolar macrophages. Immunohistochemical analysis indicated that foamy alveolar macrophages in the Clara cell-ablated group that inhaled crystalline silica overexpress CD36 and LOX-1, indicating upregulation of scavenger receptors of alveolar macrophages. These cells also express MMP-2, -9 and -12, suggesting increased gelatinolytic and elastolytic activities. Our findings suggest that Clara cells not only inhibit infiltration of alveolar macrophages but also their phagocytotic and gelatinolytic functions in silica-induced pulmonary injury.