Development of A Human Lung Co-Culture Model System for Hazard Identification of Aerosolized Particles

Abstract

There is a growing need for lung cell culture model systems to assess potential hazards associated with aerosolized particles. In vivo models for safety testing are being phased out due to increased social, financial, and time pressures. In vitro cell cultures have shown promise as surrogates in screening assays when multiple substances require preliminary information on toxicity. We present an exposure apparatus composed two of critical parts. The first part is an aerosol generator that delivers liquid and/or solid aerosols in the size range of 1–3 lm in diameter. The second part is a co-culture system of upper respiratory tract mammalian cells including epithelial, macrophage, and dendritic cells. The aerosols used in the development of this apparatus include trimellitic anhydride (i.e. solid powder) and toluene-2,4-diisocyanate (i.e. liquid droplet). Both aerosols
have been shown to induce inflammation and/or cause irritation in the respiratory tract. This study focuses on comparing the cellular effects before and after aerosol exposure. Specific cytokine expressions of exposed cells compared to control cell populations are as follows: MIP-1 (increase by 50%), TNF-a (increase by 75%), and IL-1b (increase by 20%). The overarching goal is to develop a high-throughput co-culture screening
system that could be used in conjunction with current in vivo test models.