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Toxicologic Pathology, Vol. 32, No. 3, 351-356 (2004)
DOI: 10.1080/01926230490431466

Emphysema and Metalloelastase Expression in Mouse Lung Induced by Cigarette Smoke

Samuel Santos Valença

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

Katia Da Hora

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

Paulo Castro

Department of Biological Chemistry, Institute of Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Vera Gonçalves Moraes

Department of Biological Chemistry, Institute of Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Laís Carvalho

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, lcporto{at}uerj.br

Luís Cristó Vão De Moraes Sobrino Porto

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

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.

Key Words: Cigarette smoke • emphysema • extracellular matrix • metalloelastase • morphometry.

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