Representative lung micrographs and TGF- mRNA expression of p66Shc−/− mice and WT mice exposed to CS for 7 months.

<p>(A) and (D) are lung micrographs of a p66Shc−/− mouse at 7 months after CS exposure. (B) and (D) show morphologic appearance of peribronchiolar fibrosis, characterized by a progressive deposition of collagen expanding into contiguous alveolar septa. (B) and (C) represent higher magnifications of (A). These micrographs show intraseptal collagen accumulation (“sea green”) (arrowheads) and alveolar lumens, which are lined by hyperplastic epithelial cells and filled with macrophages. These macrophages are often multinucleated. (E) is representative lung parenchyma from an air-control p66Shc−/− mouse showing a normal appearance. (F) is a lung parenchyma from a WT mouse exposed to CS for 7 months, showing air space enlargements (emphysema) (*). Masson’s trichrome stain. Scale bars = 40 μm. Immunohistochemical staining for transforming growth factor-beta (TGF-) on lung sections of WT (G) and p66Shc−/− (H) mice at 7 months. (I) Real-time PCR analysis of mRNA for TGF-β carried out on lungs from six mice for each experimental group at 7 month after CS exposure. Values are corrected for 18S rRNA and normalised to a median control value of 1.0. Data are presented as meanSD. * P< 0.05 with air-control values of the same genotype.