Cigarette smoke exposure produces more evidence of emphysema in B6C3F1 mice than in F344 rats

Abstract

Cigarette smoke (CS) causes pulmonary emphysema in humans, but results of previous studies on CS-exposed laboratory animals have been equivocal and have not clearly demonstrated progression of the disease. In this study, morphometry and histopathology were used to assess emphysema in the lungs of B6C3F1 mice and Fischer-344 rats. The animals were exposed, whole-body, to CS at a concentration of 250 mg total particulate matter/m3 for 6 h/day, 5 days/week, for either 7 or 13 months. Morphometry included measurements of parenchymal air space enlargement (alveolar septa mean linear intercept [Lm], volume density of alveolar air space [VVair]), and tissue loss (volume density of alveolar septa [VVspt]). In addition, centriacinar intra-alveolar inflammatory cells were counted to assess species differences in the type of inflammatory response associated with CS exposure. In mice, many of the morphometric parameters indicating emphysema differed significantly between CS-exposed and control animals. In CS-exposed rats, only some of the parameters differed significantly from control values. The Lm in both CS-exposed mice and rats was increased at 7 and 13 months, indicating an enlargement of parenchymal air spaces, but the VVair was increased significantly only in CS-exposed mice. The VVspt was decreased at both time points in mice, but not in rats, indicating damage to the structural integrity of parenchyma. Morphologic evidence of tissue destruction in the mice included alveoli that were irregular in size and shape and alveoli with multiple foci of septal discontinuities and isolated septal fragments. Morphometric differences in the mice at 13 months were greater than at 7 months, suggesting a progression of the disease. Inflammatory lesions within the lungs of mice contained significantly more neutrophils than those lesions in rats. These results suggest that B6C3F1 mice are more susceptible than F344-rats to the induction of emphysema by this CS exposure regimen and that in mice the emphysema may be progressive. Furthermore, the type of inflammatory response may be a determining factor for species differences in susceptibility to emphysema induction by CS exposure.

Pulmonary Prostacyclin Synthase Overexpression Chemoprevents Tobacco Smoke Lung Carcinogenesis in Mice

“…After an acclimatization period, mice were placed in wire-bottomed cages in the smoke exposure chamber. The mice were exposed to diluted and slightly aged mainstream cigarette smoke generated from burning 1R3 reference cigarettes (Kentucky Tobacco Research and Development Center, University of Kentucky, Lexington, KY) as described previously (5,16). Mice were exposed to smoke concentrations of 100 mg total particulate matter/m 3 for the first week, and then the concentration was increased to 250 mg total particulate matter/m 3 for the remainder of the exposure.…”

Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction

“…However, they appear to be relatively resistant to the induction of emphysema-like lesions. Using morphometry and histopathology to assess and compare emphysema development in mice and rats, significant differences were demonstrated [214]. In B6C3F 1 mice, many of the morphometric parameters used to assess emphysema-like lesions differed significantly between exposed and nonexposed animals.…”

“…Enlarged alveolar spaces and increased alveolar duct area are found after 3-6 months of tobacco smoke exposure in susceptible strains, such as B6C3F 1 mice [214]. The length of time required to produce emphysema is usually .4 months, depending upon the method of exposure, cigarette dose and species [215][216][217].…”

Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke-induced emphysema

“…The number of recent reports on the pathophysiology of emphysematous animal models has increased rapidly, but none of them has tested the presence of hypercapnia/hypoxemia ( (Mahadeva et al 2002), see discussion in reference (March et al 2006b)). The emphysema of C3H/HeN, A/J, and C57BL/6 mice induced by chronic CS exposure (16 wk) has been investigated, and the results shown that the emphysema susceptibility among these strains has been ranked as C3H/HeN > A/J > C57BL/ 6; female mice are particularly affected (March et al 1999(March et al , 2006a(March et al , 2006bGuerassimov et al 2004). Thus, we hypothesized that female C3H/HeN mice chronically exposed to CS would display the major characteristics seen in hypercapnic COPD patients, including: (1) emphysema, (2) hypercapnia, (3) rapid breathing at rest, and (4) AVR to hypoxia and hypercapnia.…”