CONCLUSION

     Ambient airborne particles are complex environmental mixtures that can have damaging effects on the mammalian lungs. These particles contain chemical and elemental materials which can be directly toxic to the resident and infiltrating cell populations. Once deposited, this material can solubilize in the aqueous extracellular lining fluid resulting in chemical toxicity to nearby cells. As well, phagocytosis by the alveolar macrophages can increase the bioavailibility of these chemical and elemental components. Using several cell culture models, we have demonstrated some of the toxic potential of environmental particulate preparations.

     Single cell culture models (fibroblast, epithelial and mesothelial cells) were used to demonstrate the toxicity of the different particle fractions. Increasing concentration of particulate preparations were shown to be toxic towards these pulmonary cell lines. As well, fractionation of these particles (water extraction) demonstrated that both the soluble and insoluble fractions were toxic towards pulmonary cells. We have also studied the role of the lung macrophage in modulating the toxicity of particles towards other cells. Using a cell culture model incorporating freshly isolated lung macrophages and suitable transgenic CAT reporter cells, we have demonstrated that macrophages can increase the bioavailability of xenobiotics from the particulate preparations, reflected in the magnified biological responses in a secondary reporter target cell. We have speculated that macrophages may bioactivate xenobiotics present in the particulate preparations to mutagenic or carcinogenic compounds. Macrophage conditioned culture medium should be analyzed for these metabolites in order to confirm or refute this hypothesis.

     Note that individual cell types present in different regions of the lung could respond differently to the same stimulus. Therefore, the development of transgenic pulmonary cell lines may be more directly relevant to the effects of particles on the lungs. Also, although we have studied the role of the alveolar macrophage in modulating the bioavailability of xenobiotics, the neutrophil is an important cell type in inflammatory reactions of the lungs. Development of cell culture models incorporating neutrophils may help to provide information on the effects of particle toxicity towards the infected lungs.