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

• Published in: American journal of respiratory and critical care medicine 2004-11, Vol.170 (9), p.974-980
• Main Authors: Guerassimov, Alexei, Hoshino, Yuma, Takubo, Yasutaka, Turcotte, Antony, Yamamoto, Midori, Ghezzo, Heberto, Triantafillopoulos, Alexandra, Whittaker, Kevin, Hoidal, John R, Cosio, Manuel G
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Biopsy, Needle; Chemokines - analysis; Chemokines - metabolism; Clinical death. Palliative care. Organ gift and preservation; Disease Models, Animal; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Inflammation Mediators - analysis; Intensive care medicine; Lung - pathology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred Strains - classification; Probability; Pulmonary Emphysema - etiology; Pulmonary Emphysema - physiopathology; Respiratory Function Tests; Severity of Illness Index; Species Specificity; Tobacco Smoke Pollution - adverse effects; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200309-1270OC

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.