title: Foam cell formation of alveolar macrophages in Clara cell ablated mice inhaling crystalline silica.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan. yatera@med.uoeh-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Heung-Nam
authors.initials: HN
authors.lastname: Kim
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Myojo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
mesh_terms: D000393:Air Pollutants; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D019570:Inhalation Exposure; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009281:Naphthalenes; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D018955:CD36 Antigens; D009281:Naphthalenes; C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; D012822:Silicon Dioxide; D020782:Matrix Metalloproteinases