Pulmonary Inflammatory Reaction and Structural Changes Induced by Cigarette Smoke Exposure in the Guinea Pig

Abstract

Cigarette smoke (CS) induces an inflammatory process in the lung that may underlie the development of chronic obstructive pulmonary disease (COPD). The nature and characteristics of this process have not been fully established in animal models. We aimed to evaluate the pulmonary inflammatory reaction and its involvement in structural changes in guinea pigs chronically exposed to CS. 19 Hartley guinea pigs were exposed to 7 cigarettes/day, during 3 or 6 months. 18 control guinea pigs were sham-exposed. Numbers of neutrophils, macrophages and eosinophils and lymphoid follicles were assessed in different lung structures. Airway and vessel morphometry, alveolar space size and collagen deposition were also quantified. After 6 months of exposure, CS-exposed guinea pigs showed increased numbers of neutrophils, macrophages and eosinophils in the airways, intrapulmonary vessels and alveolar septa, as well as lymphoid follicles. Increased numbers of muscularized intrapulmonary vessels were apparent at 3 months. After 6 months of exposure, the airway wall thickened and the alveolar space size increased. Collagen deposition was also apparent in airway walls and alveolar septa after 6 months' exposure. The magnitude of airway wall-thickening correlated with the number of infiltrating inflammatory cells, and the extension of collagen deposition correlated with alveolar space size. We conclude that in the guinea pig, 6 months of CS exposure induces inflammatory cell infiltrate in lung structures, at an intensity that correlates with airway remodelling. These changes resemble those observed in COPD, thus endorsing the pathogenic role of CS and the usefulness of this animal model for its study.

The vascular bed in COPD: pulmonary hypertension and pulmonary vascular alterations

“…Taken together, these facts suggest that increased shear stress in the pulmonary arteries, in combination with vascular injury, can induce neointimal lesions. In truth, tobacco smoke products may directly cause endothelial cell dysfunction, resulting in impaired release of endothelial nitric oxide synthase [18], increased expression of VEGF [44], and increased numbers of inflammatory cells [45]. Moreover, endothelial cell dysfunction-related factors have been shown, in principle, to be able to affect vascular SMC growth [46].…”

Pulmonary vasculature in COPD: The silent component

“…Studies conducted in smokers without airflow obstruction have shown that these individuals present remodelling in pulmonary arteries, impairment of endothelial function, reduced expression of eNOS, increased VEGF expression, inflammatory cell infiltrate and gene expression of cytokines and angiogenic mediators, which are indistinguishable from those seen in patients with mild‐to‐moderate COPD and clearly differ from nonsmokers. In addition, experimental animal models chronically exposed to cigarette smoke develop pulmonary vascular changes similar to those seen in COPD patients; endothelial dysfunction, vessel remodelling, vascular inflammation and PH . In these animal models, cigarette smoke exposure induces changes in gene expression of VEGF, VEGF receptor‐1, ET‐1 and inducible NOS, mediators that regulate vascular cell growth and vessel contraction and are likely involved in the pathogenesis of pulmonary vascular changes of COPD.…”

Tobacco smoke induced COPD/emphysema in the animal model—are we all on the same page?

“…While mice are surely favored for their wide variety of applicable gene expression manipulations, it remains difficult to standardize measurements of pulmonary function to assess disease parameters. The guinea pig model is also occasionally applied, mainly by one group of investigators (Simani et al, 1974; Wright and Churg, 1990, 2002; Wright and Sun, 1994, 1999; Wright et al, 2002, 2011) though increased inflammatory cells and muscularization of pulmonary vessels was recently documented (Dominguez-Fandos et al, 2012). The rat is a favorable model, since measurable emphysematous changes which further progress can be detected after only 2 months of smoke exposure (Kratzer et al, 2013).…”