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American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 1596-1603, (2002)
© 2002 American Thoracic Society

Original Article

{alpha}1-Antitrypsin Determines the Pattern of Emphysema and Function in Tobacco Smoke–exposed Mice

Parallels with Human Disease

Yasutaka Takubo*, Alexei Guerassimov*, Heberto Ghezzo, Alexandra Triantafillopoulos, Jason H. T. Bates, John R. Hoidal and Manuel G. Cosio

Respiratory Division, Royal Victoria Hospital, Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada; Department of Medicine and Molecular Physiology and Biophysics, Colchester Research Facility, University of Vermont, Colchester, Vermont; and Division of Respiratory, Clinical Care, and Occupational Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah

Correspondence and requests for reprints should be addressed to M. G. Cosio, M.D., McGill University, Royal Victoria Hospital, Respiratory Division, Room L4.11, 687 Pine Avenue West, Montreal, PQ, H3A 1A1 Canada. E-mail: manuel.cosio{at}muhc.mcgill.ca

Cigarette smoking in humans is associated with various patterns of emphysema and functional consequences. We tested the hypothesis that variations in {alpha}1-antitrypsin expression modulate the pattern of emphysema and functional consequences in cigarette smoke–exposed mice. We compared the effects of up to 6 months of cigarette smoke exposure in C57BL/6J (C57) mice and in low-{alpha}1-antitrypsin, C57BL/6J pa+/pa+ (pallid) mice. At the end of the experiment, we determined lung mechanical properties, the extent (mean linear intercept) and type of emphysema, and the cellular inflammatory response. After 4 months of cigarette smoking, pallid smoking mice, but not C57 smoking mice, had a significant increase in mean linear intercept. After 6 months of smoke exposure, C57 smoking mice and pallid smoking mice had similar degrees of emphysema. The pattern of emphysema in pallid smoking mice was more diffuse than in C57 smoking mice, affecting all airspaces. Pallid mice, but not C57 mice, developed a T cell inflammation in the alveolar wall after 6 months of smoking (p < 0.01). Although lung compliance was not changed in C57 smoking mice after smoke exposure, it increased significantly in pallid smoking mice over the 6 months of exposure (p < 0.0082). In summary, cigarette smoking induces emphysema in C57 and pallid mice, but the emphysema, inflammatory infiltrate, and resulting physiologic abnormalities were substantially different in the two strains, with the C57 and pallid mice exhibiting features similar to centrilobular and panlobular emphysema, respectively.

Key Words: {alpha}1-antitrypsin • emphysema • lung mechanics • mice • smoking




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