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

Toxicol Sci. 2015 Sep;147(1):75-83. doi: 10.1093/toxsci/kfv108. Epub 2015 Jun 1.

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.

Keywords: alveolar destruction; cigarette smoke; metalloprotease; mouse strains.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Female
  • Male
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Neutrophils / metabolism
  • Pneumonia / chemically induced*
  • Pneumonia / pathology*
  • Pulmonary Alveoli / pathology
  • Pulmonary Emphysema / chemically induced*
  • Pulmonary Emphysema / pathology*
  • Sex Characteristics
  • Smoke / adverse effects*
  • Species Specificity
  • Tobacco Products*
  • Tobacco*

Substances

  • Smoke
  • Matrix Metalloproteinases