Pulmonary inflammation and fibrosis in a murine model of asbestosis and silicosis. Possible role of tumor necrosis factor.
Prolonged asbestos and silica inhalation is associated with pulmonary inflammation and fibrosis. Several studies suggest that TNF may play a role in the development of inflammation and fibrosis. We studied TNF production in a murine model of asbestosis and silicosis. Asbestos fibers caused a significant inflammatory response at two weeks and pulmonary fibrosis beginning at one month. Pulmonary inflammation was principally caused by an accumulation of neutrophils (0.88 x 10(5) neutrophils/compared to 0.05 x 10(5) in controls). TNF production by bronchoalveolar cells was higher in asbestos-instilled mice at two weeks, but was significantly diminished in older mice. Pulmonary inflammation was observed until six months in silica-instilled mice. Neutrophils were also the principal protagonists of the inflammation. In this group, severe fibrosis was observed at two weeks. TNF production in silica-instilled mice was similar to controls, possibly due to the presence of large numbers of neutrophils (3.3 x 10(5)/lavage) that could adsorb TNF. In vitro experiments showed an augmentation of TNF production by bronchoalveolar cells in the presence of silica. Taken together, our data suggest that asbestos and silica stimulate alveolar macrophages to produce TNF, which can be involved in pulmonary inflammation and fibrosis.
Bissonnette
E
E
Immunology Division, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
Rola-Pleszczynski
M
M
D000818:Animals; D001195:Asbestosis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology; D012829:Silicosis / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha