title: Alveolar wall apoptosis causes lung destruction and emphysematous changes.
abstract: Pulmonary emphysema is characterized by alveolar wall destruction and airspace enlargement. Recent evidence indicates that epithelial or endothelial apoptosis may be involved in the pathogenesis of emphysema. Here, we describe the induction of emphysematous changes, including airspace enlargement, alveolar wall destruction, and enhanced lung distensibility, in mice receiving a single intratracheal injection of active caspase-3 and Chariot, a newly developed protein transfection reagent. Epithelial apoptosis and enhanced elastolytic activity (optimal at pH 5.5) in bronchoalveolar lavage were noted. Emphysematous changes were also generated in mice receiving an intratracheal injection of nodularin, a proapoptotic serine/threonine kinase inhibitor. This murine model provides direct evidence that confirms that alveolar wall apoptosis causes emphysematous changes. Furthermore, this simple technique for protein transfection of lung tissue can be used in a variety of future applications.
authors.affiliation: First Department of Medicine, Tokyo Women's Medical University, Japan. kaoshiba@chi.twmu.ac.jp
authors.forename: Kazutetsu
authors.initials: K
authors.lastname: Aoshiba
authors.forename: Naoko
authors.initials: N
authors.lastname: Yokohori
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D004646:Emphysema / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D014162:Transfection / Q000379:methods
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D004549:Elastin; D010196:Pancreatic Elastase; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases