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Published ahead of print on July 28, 2004, doi:10.1164/rccm.200309-1270OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 9, November 2004, 974-980

A more recent version of this article appeared on November 1, 2004
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Submitted on September 12, 2003
Accepted on July 26, 2004

The Development of Emphysema in Cigarette Smoke Exposed Mice is Strain Dependent

Alexei Guerassimov1, Yuma Hoshino1, Yasutaka Takubo1, Antony Turcotte1, Midori Yamamoto1, Herberto Ghezzo1, Alexandra Triantafillopoulos1, Kevin Whittaker1, John R Hoidal2, and Manuel G Cosio1*

1 Respiratory Division, Royal Victoria Hospital, Meakins-Christie Laboratories, McGill University, Montreal, PQ, Canada, 2 Division of Respiratory, Clinical Care and Occupational Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA

* To whom correspondence should be addressed. E-mail: manuel.cosio{at}muhc.mcgill.ca.

Only 20% of smokers develop COPD. 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, since 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 six months. Elastance (Htis), the extent of emphysema (Lm) and the inflammatory cell and cytokines 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 up-regulation of Th:1 cytokines while in the C57BL/6/J and NZWlac/J cytokines did not change or were down-regulated. We conclude that Lm, elastance and inflammation are features 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: Mice, emphysema, immunity, elastance, genomics.




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