Correlation of Cigarette Smoke-Induced Pulmonary Inflammation and Emphysema in C3H and C57Bl/6 Mice

Abstract

Cigarette smoke (CS)-exposed mice have been used to model airway inflammation and emphesema in humans; however, the impact of exposure duration, sex, and strain differences in susceptibility to progression of airway inflammation and to emphesema are poorly investigated. This study was designed to determine the association between inflammation and emphysema by exposing 2 strains of mice, C3H/HeN (C3H) and C57BL/6 (Bl/6), to filtered air (FA) or CS for 10, 16, or 22 weeks. Both genders and strains of CS-exposed mice developed pulmonary inflammation as characterized by cell counts in the bronchoalveolar lavage fluid (BALF) and the levels of matrix metalloproteinases (MMPs) in the BALF. CS exposure caused persistently higher number of BALF macrophages in C3H compared to BL/6 mice, while more BALF neutrophils and persistently higher MMP-2 and MMP-9 levels were observed in BL/6 mice. The mean linear intercept (Lm) increased progressively by 26%, 33%, and 55% at 10, 16, and 22 weeks, respectively, in CS-exposed C3H mice compared to the matched air controls. In BL/6 mice, although CS exposure also increased the Lm compared to FA controls, no further increase in Lm beyond the levels observed at 16 weeks of exposure was observed by 22 weeks. These findings suggest that extent of inflammation is not associated with severity of emphysema and underscores the importance of carefully selecting the mouse strains and endpoints when exploring effective treatments for emphesema.

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development

“…However, such cells are difficult to stably transfect to reduce XPC expression in a consistent manner, which is why we have chosen the present model, complemented with in vivo experiments for relevance. Although our study was not sufficiently powered, we, similar to others, noted an effect of sex on the magnitude of emphysema development in response to CS (28), even in this genetically heterogeneous mouse strain, with male mice being more susceptible to CS than female counterparts, regardless of XPC levels.…”

Early Postnatal Secondhand Smoke Exposure Disrupts Bacterial Clearance and Abolishes Immune Responses in Muco-Obstructive Lung Disease

“…The gender-specific responses to SHS have been reported previously. In comparison with tobacco smoke-exposed adult males, the females exhibit exaggerated allergic responses (50), alveolar airspace enlargement (51), and increased airway remodeling (52,53). Interestingly, our key findings, in particular neutrophil counts, cytokine levels, and mucous cell metaplasia, which form the basis of our study, followed similar trends for both genders (Supplemental Tables III, IV).…”

Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease

“…Evidence suggests that increased small airway wall remodeling is observed in female compared with male mice (24,25). Data on airspace enlargement are less conclusive, with reports that cigarette smoke-induced emphysema occurs more readily in female compared with male mice, whereas other studies did not observe differences between sexes (26,27). Clearly, further studies are warranted to assess sex differences in animal models of COPD.…”