title: Emphysema and metalloelastase expression in mouse lung induced by cigarette smoke.
abstract: Cigarette smoke (CS) causes pulmonary emphysema in humans and elastin degradation plays a key role in its pathogenesis. Previous studies on CS-exposed animals have been equivocal and have not clearly demonstrated the progression of the disease. In this study, morphometry was used to assess lung modifications to alveolar septa, airspaces, elastic and collagen fibers, and alveolar macrophages. Male (n = 40) C57/BL6 mice were exposed 3 times/day, whole body, to CS from three cigarettes for 10, 20, 30, or 60 days. Control groups (n = 10) were sham-smoked or received no exposure (day 0, n = 10). Morphometry included measurements of volume fraction of alveolar septa and airspaces, elastic and collagen fibers, and surface fraction of elastic fibers and alveolar septa. Morphometrical differences in mice after 60 days of exposure were greater than those after 10, 20, or 30 days, suggesting a progression of the disease. Inflammatory lesions in the lungs of mice contained significantly more metalloelastase (MMP-12) in macrophages at 10, 20, and 30 days than in controls of mice exposed for 60 days. These results suggest that elastin degradation took place during development of pulmonary changes in mice exposed to CS, and activation of MMPs specific for elastin may be a determining factor for susceptibility to emphysema.
authors.affiliation: Department of Histology and Embryology, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Av. Prof. Manoel de Abreu 444, 20551-170, Rio de Janeiro, Brazil.
authors.forename: Samuel Santos
authors.initials: SS
authors.lastname: Valença
authors.forename: Katia
authors.initials: K
authors.lastname: da Hora
authors.forename: Paulo
authors.initials: P
authors.lastname: Castro
authors.forename: Vera Gonçalves
authors.initials: VG
authors.lastname: Moraes
authors.forename: Laís
authors.initials: L
authors.lastname: Carvalho
authors.forename: Luís Cristóvão de Moraes Sobrino
authors.initials: LC
authors.lastname: Porto
mesh_terms: D000818:Animals; D003094:Collagen / Q000187:drug effects; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004549:Elastin / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000201:enzymology; D008297:Male; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011656:Pulmonary Emphysema / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D012906:Smoke; D003094:Collagen; D004549:Elastin; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12