The use of precision-cut lung slices to assess inflammation, parenchymal damage, and collagen deposition: three markers of tobacco exposure-induced pulmonary toxicity
The Family Smoking Prevention and Tobacco Control Act (TCA) gives the Food and Drug Administration (FDA) broad authority to regulate tobacco products. The FDA-Center for Tobacco Products (CTP) calls for several research priority areas, including in vitro models and assays that will assess tobacco constituent safety and comparative product toxicity. Precision-cut lung slices (PCLS) retain normal lung architecture and endogenous cell types and have been effective in assessing acute pulmonary toxicity. Having demonstrated release of traditional leakage markers, inflammation, and tissue damage, recent advances in PCLS culture and choice of biomarkers suggest suitability for detecting specific events that contribute to the etiology of tobacco-induced chronic obstructive pulmonary disease (COPD). PCLS were exposed to various compounds known to cause acute and chronic pulmonary lesions. Acute toxicity was assessed via cytokine level, protein content, and the overt destruction of parenchymal tissue. Chronic exposures also included quantifying activated macrophages and assessing a marker of fibrosis (in addition to general histopathological evaluation). Acute toxicity elicited a rapid increase in cytokine levels, reduction in tissue leakage markers, and overt parenchymal damage. Chronic exposures lasting up to several weeks also resulted in decreased tissue viability, increased numbers (and location of) activated macrophages (ED-1 positive cells) and deposition of collagen. In summary, PCLS data from various chemical assessment studies are compiled to highlight the changes in different markers of acute and chronic toxicity, as related to the known events of tobacco-induced COPD etiology. It is expected that PCLS will prove to be a valuable tool in elucidating both acute and chronic effects of compounds found in tobacco or modified risk tobacco products such as e-cigarettes.