title: Nanosized aluminum altered immune function.
abstract: On the basis of their uses in jet fuels and munitions, the most likely scenario for aluminum nanoparticle (NP) exposure is inhalation. NPs have been shown to be capable of penetrating deep into the alveolar regions of the lung, and therefore human alveolar macrophages (U937) with human type II pneumocytes (A549) were cultured together and exposed to NPs dispersed in an artificial lung surfactant to more accurately mimic the lung microenvironment. Two types of NPs were evaluated: aluminum (Al) and aluminum oxide (Al2O3). Following a 24-h incubation, cell viability was assessed using MTS, and mild toxicity was observed at higher doses with the U937 cells affected more than the A549. Since the U937 cells provided protection from NP toxicity, the cocultures were exposed to a benign concentration of NPs and infected with the respiratory pathogen community-associated methicillin-resistant Staphylococcus aureus (ca-MRSA) to determine any changes in cellular function. Phagocytosis assays demonstrated that the NPs impaired phagocytic function, and bacterial growth curves confirmed that this reduction in phagocytosis was not related to NP-bacteria interactions. Furthermore, NFkappaB PCR arrays and an IL-6 and TNF-alpha real time PCR demonstrated that both types of NPs altered immune response activation. This change was confirmed by ELISA assays that evaluated the secretion of IL-6, IL-8, IL-10, IL-1beta, and TNF-alpha and illustrated that the NPs repressed secretion of these cytokines. Therefore, although the NPs were not toxic to the cells, they did impair the cell's natural ability to respond to a respiratory pathogen regardless of NP composition.
authors.affiliation: Applied Biotechnology Branch, Human Effectiveness Directorate, Air Force Research Laboratory, Wright-Patterson AFB, Ohio, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Braydich-Stolle
authors.forename: Janice L
authors.initials: JL
authors.lastname: Speshock
authors.forename: Alicia
authors.initials: A
authors.lastname: Castle
authors.forename: Marcus
authors.initials: M
authors.lastname: Smith
authors.forename: Richard C
authors.initials: RC
authors.lastname: Murdock
authors.forename: Saber M
authors.initials: SM
authors.lastname: Hussain
mesh_terms: D000042:Absorption; D000535:Aluminum / Q000737:chemistry* / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000382:microbiology
chemical_list: D000535:Aluminum