Increased phosphorylated extracellular signal-regulated kinase immunoreactivity associated with proliferative and morphologic lung alterations after chrysotile asbestos inhalation in mice

Activation of extracellular signal-regulated kinases (ERK) has been associa ted with the advent of asbestos-associated apoptosis and proliferation in m esothelial and alveolar epithelial cells and may be linked to the developme nt of pulmonary fibrosis, The objective of studies here was to characterize the development of inflammation, cellular proliferation, and fibrosis in a sbestos-exposed wC57Bl/6 mice in relationship to patterns of ERK phosphoryl ation. Inflammation occurred after 10 and 20 days of asbestos exposure as e videnced by increases in total protein and neutrophils in bronchoalveolar l avage fluid. Increases in cell proliferation were observed at 30 days in br onchiolar epithella and at 4, 14, and 30 days in the alveolar compartment o f the lung. Trichromepositive focal lesions of pulmonary fibrosis developed at 30 days in the absence of elevations in lung hydroxyproline or procolla gen mRNA levels. Striking increases in ERK phosphorylation were observed wi thin pulmonary epithelial cells at sites of developing fibrotic lesions aft er 14 and 30 days of inhalation. In addition to characterizing a murine inh alation model of asbestosis, we provide the first evidence showing activati on of ERK signaling within lung epithelium is vivo, following inhalation of asbestos fibers.