The relationship between elastin degradation and emphysema is well known. Recent evidence suggests that a complex process of pulmonary remodeling occurs within the emphysematous lung. The aim of this study was to assess the extent of extracellular matrix remodeling in emphysema by ultrastructural examination of elastin and collagen templates in an animal model of emphysema and in human emphysematous lungs. Emphysema was induced in rats by the intratracheal administration of porcine pancreatic elastase. Human lung samples were obtained at surgical resection for lung carcinoma. Emphysema was confirmed morphometrically and quantitated using the mean linear intercept. Matching sections were treated with sodium hydroxide and formic acid to expose collagen and elastin templates, respectively. Scanning electron microscopy with stereo-pair imaging allowed three-dimensional visualization of the exposed templates. In emphysematous lungs from both sources, sheets of elastin were disrupted and perforated with multiple fenestrations. In elastase-induced emphysema, this disintegration was accompanied by a marked increase in thickness of collagen fibrils, which contrasted with the fine fibrillar network of control lungs. Similarly, a pattern of thickened fibrils and disorganized deposition of collagen was observed in human lungs. In conclusion, these findings support the novel concept of increased collagen deposition and aberrant collagen remodeling in the pathogenesis of emphysema.
University College Dublin ->