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The Development of Emphysema in Cigarette Smoke-exposed Mice Is Strain Dependent

Respiratory Division, Royal Victoria Hospital, Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada; 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 Manuel 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

Only 20% of smokers develop chronic obstructive pulmonary disease. An important determinant of susceptibility is genomic variation. We undertook this study to define strains of mice with different susceptibilities for the development of smoking-induced emphysema because they could help identify genetic factors of susceptibility. NZWLac/J, C57BL6/J, A/J, SJ/L, and AKR/J strains were exposed to cigarette smoke for 6 months. Elastance (Htis), the extent of emphysema (mean linear intercept [Lm]), and the inflammatory cell and cytokine response were measured. NZWLac/J had no change in Lm or Htis (resistant). C57BL6/J, A/J, and SJ/L increased Lm, but not Htis (mildly susceptible). AKR/J increased Lm and Htis (super-susceptible). Only AKR/J had significant inflammation comprising macrophages, neutrophils, and T cells. The AKR/J showed an upregulation of Th1 cytokines whereas in the C57BL/6/J and NZWlac/J, cytokines did not change or were downregulated. We conclude that Lm, elastance, and inflammation are features that are needed to phenotype emphysema in mice. The inflammatory cell and cytokine profile may be an important determinant of the phenotype in response to cigarette smoke exposure. The identification of resistant and susceptible strains for the development of emphysema could be useful for genomic studies of emphysema susceptibility in mice and eventually in humans.

Key Words: elastance • emphysema • immunity • genomics • mice

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