ABSTRACT

     Development of in vitro models for studying pulmonary cell dynamics in the face of environmental exposure is an important component of respiratory toxicology. In vitro systems can model direct cytotoxic effects and cell-cell interactions in the lungs. This information can aid in interpreting results generated from in vivo experiments or from epidemiological studies. To begin studying the toxic effects of airborne particulate material in the mammalian lung, several cell culture models were used to rank the toxicity of different particulate preparations. Single cell culture models were used to measure the direct cytotoxicity of air particulate standards towards individual cell types. Co- culture models were used to study the ability of the alveolar macrophage to modulate the toxicity of these particles towards other cell types. Following successful assembly of a sequential cell culture model incorporating CAT transgenic cell lines and isolated bronchoalveolar macrophages, it was determined that macrophages can increase the availability of metals and PAHs from air particulate material to surrounding cell populations. This modulation of cytotoxic effects has important implications with respect to lung toxicology. This indicates that cell-cell interactions in the airways and alveoli can modulate toxicity following exposure to ambient airborne particulate material.