IMMUNE SUPPRESSION IN MRSA- INFECTED HUMANALVEOLAR CO-CULTURES TREATED WITH ALUMINUMNANOPARTICLES

摘要

The goal of this study was to evaluate the biological response following exposure to aluminum nanoparticles (Al NP). Based on their uses in jet fuels and munitions, the most likely scenario for exposure is inhalation. Since nanoparticles have been shown to be capable of penetrating deep into the alveolar regions of the lung, we cultured human alveolar macrophages (U937) with human type I pneumocytes (A549) and then exposed them to Al NPs (0-500 μg/ml) dispersed in an artificial lung surfactant to create an in vitro model which simulated the lung microenvironment. Three types of Al NPs were evaluated and they were aluminum (Al), aluminum oxide (Al_2O_3) and aluminum oleic acid (Al-OA). Following a 24 h incubation, cell viability was assessed using MTS, to evaluate mitochondrial function, and Biovision's Live Cell/Dead Cell kit. This data illustrated that there was mild toxicity at higher doses and that the cells affected by the NPs were the macrophages. Since the immune cells in the lung protect the epithelial cells, the co-cultures were exposed to a benign concentration of Al NPs and then infected with the pathogen MRSA. Bacterial growth curves demonstrated that MRSA growth was not impacted by any of the aluminum nanoparticles. Additionally, phagocytosis assays demonstrated the Al and Al-OA impaired phagocytic function. Furthermore, NFkB and cytokine PCR arrays demonstrated that all three types of Al NPs altered the activation of the normal immune response. This change was further confirmed by ELISA assays which evaluated the secretion of IL-6, IL-8, IL-10, IL-1β, and TNFα. In all cases, the presence of all types of Al NPs repressed the co-cultures' ability to secrete cytokines. Clearance#: 88ABW-2008-0134