The Development of Cigarette Smoke-Induced Lung Lesions in Two Strains of Mice

We reported that ICR mice are resistant to chronic smoke while C57Bl/6J and DBA/2 mice develop emphysema. In this study we investigated the kinetics of cigarette smoke-induced emphysema and of airways changes in the two sensitive strains. C57Bl/6J and DBA/2 mice were exposed to either the smoke of 3 cigarettes/day (Virginia: 12 mg of tar and 0.9 mg of nicotine) 5 days/week for 1, 3, 6, 8, 10 and 12 months or to room air (controls). At these time intervals animals were sacrificed and the lungs assessed for emphysema (Lm, SA/VL) and for goblet cell metaplasia (GCM on PAS stained sections). Immunohistochemistry included MUC5AC, IL-4 and IL-13. Electron microscopy (EM) was also used. The percentage of C57Bl/6J mice with emphysema increased with time reaching 100% at 6 months and remained on this level. From 3 months onwards the Lm of the smoke exposed mice was greater and the SA/VL lower than in the controls. The percentage of DBA/2 mice with emphysema mice increased up to 6 months (83%) but decreased thereafter. At all time points the percentage of C57Bl/6J mice with emphysema was greater than that of DBA/2 mice. The percentage of C57Bl/6J mice with GCM increased from 40% at 1 month to 91% at 3 months and 100% at 6 months but decreased thereafter. In the DBA/2 group the percentage of mice with GCM was very low and occurred late (14% at 8 months and 25% at 10 months). In both strains in the responding animals there was a positive staining for IL-4, IL-13 and MUC 5 AC at 1, 3 and 8 months. Scanning EM showed areas of deciliation at 3 and 12 months in both strains. At transmission EM, the deciliated areas were characterized by de-differentiated cells with microvilli which have the potential to restore the normal epithelium. In apparently normally ciliated areas, a disorientation of the axonemal shaft was also observed. Thus, there was a greater response of the C57Bl/6J mice both in terms of percentage of animals with emphysema and with GCM. In the affected animals the lesions were similar in both strains. Both strains are sensitive to cigarette oxidants but only C57BL/6J mice have low BAL elastase inhibitory capacity.