Modelling COPD in mice

https://doi.org/10.1016/j.pupt.2005.02.006Get rights and content

Abstract

Chronic obstructive pulmonary disease (COPD) is characterised by persistent airflow limitation, neutrophilic inflammation, macrophage accumulation, and the production of cytokines, chemokines and proteases. Cigarette smoking is the major cause of COPD and there is currently no satisfactory therapy to help treat individuals with this disease. A better understanding of the cellular and molecular responses triggered by cigarette smoke may provide new molecular targets for the development of therapeutic agents. This brief review highlights some of the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure.

Section snippets

Which inflammatory cells are involved in the pathophysiology of COPD?

A variety of cell types are involved in the pathophysiology of COPD, including macrophages, neutrophils and T-lymphocytes. The airways, lung parenchyma, bronchoalveolar lavage fluid (BALF) and sputum of patients with COPD have elevated levels of macrophages compared with normal smokers [5], [6], [7]. There is a correlation between macrophage numbers in the airways and the severity of COPD [8]. Macrophages release inflammatory mediators including TNF-α, MCP-1, reactive oxygen species and

Proteases in COPD

Proteases regulate lung inflammation via the production of cytokines and chemokines and ultimately destroy the extracellular matrix (particularly elastin) of lung parenchyma to produce emphysema [14]. The major proteases involved in COPD include neutrophil elastase and various matrix metalloproteinases, although other serine proteases such as cysteine proteases and proteinase 3 have been implicated [2], [14], [15]. Patients with emphysema have an increase in BALF concentrations and macrophage

Modelling COPD in mice

COPD is a heterogenous disorder consisting of lung inflammation, chronic obstructive bronchiolitis, mucus plugging and emphysema (Fig. 1). Animal models are important in determining the underlying mechanisms of COPD as they address questions involving integrated whole body responses. To date, many species have been used including rodents, dogs, guinea-pigs, monkeys and sheep [23], [24], [25]. Mice offer the greatest ability to investigate the pathogenetic pathways of disease given the advances

Acute exacerbations of COPD

Acute exacerbations of COPD (AECOPD) are a common cause of morbidity and mortality in COPD patients and place a large burden on health care resources. AECOPD may be prolonged, may accelerate the progression of COPD and have a profound effect on the quality of life [37]. The cellular and molecular mechanisms underlying AECOPD are unclear, but there is an increase in neutrophils and concentrations of IL-6, IL-8, TNF-α and LTB4 in sputum during an exacerbation [38], [39] and patients who have

Summary

Cigarette smoking is the major cause of COPD and, apart from smoking cessation, there is currently no treatment that slows the progression of the disease. The characteristic features of human COPD including neutrophilia, the accumulation of macrophages and T-lymphocytes, production of cytokines and chemokines, induction of proteases and the development of emphysema can all be replicated in mice by exposure to cigarette smoke. We and others have proposed that short term responses to cigarette

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