Experimental systems for mechanistic studies of toxicant induced lung inflammation

Human breath contains a large array of complex and poorly characterized mix tures. We can measure the potential risk of these exposures at molecular, c ell, organ, organismic levels or in population. This paper emphasizes the c haracteristics of in vitro tests of lung cells and discusses the use of in vitro systems to determine the health effects of inhaled pollutants. Exposu re to gases can be performed with roller bottles fitted with modified rotat ing caps with tubing connections, or by using dishes on rocker platforms, w hich tilt back and forth to expose the cell culture to gases. Exposure of c ells may also be obtained by using very thin gas-permable membrane on which cells grow. However, it is clear that in using these systems, the culture medium constitutes a barrier between the gas and the target cells and thus does not permit a physiological approach of the toxic effects of gases. Thi s is the reason why an experimental model, using a biphasic cell culture te chnique in gas phase, was developed. We report the value and the limits of this method using bronchial cells or alveolar macrophages. Exposure of lung cells to gas pollutants or particles may be responsible for either cell in jury or cell activation associated with the overexpression of mRNA and the release of various bioactive mediators. In vitro assays have some limitatio ns, particularly because the human pulmonary response to inhaled pollutants is the result of complex interactions involving many different cell types within the lungs. However, cell culture using biphasic systems in aerobiosi s opens new ways for the research on the biological effects of gas pollutan ts. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.