title: Nanoparticles modulate surfactant protein A and D mediated protection against influenza A infection in vitro.
abstract: Numerous epidemiological and toxicological studies have indicated that respiratory infections are exacerbated following enhanced exposure to airborne particulates. Surfactant protein A (SP-A) and SP-D form an important part of the innate immune response in the lung and can interact with nanoparticles to modulate the cellular uptake of these particles. We hypothesize that this interaction will also affect the ability of these proteins to combat infections. TT1, A549 and differentiated THP-1 cells, representing the predominant cell types found in the alveolus namely alveolar type I (ATI) epithelial cells, ATII cells and macrophages, were used to examine the effect of two model nanoparticles, 100 nm amine modified (A-PS) and unmodified polystyrene (U-PS), on the ability of SP-A and SP-D to neutralize influenza A infections in vitro. Pre-incubation of low concentrations of U-PS with SP-A resulted in a reduction of SP-A anti-influenza activity in A549 cells, whereas at higher concentrations there was an increase in SP-A antiviral activity. This differential pattern of U-PS concentration on surfactant protein mediated protection against IAV was also shown with SP-D in TT1 cells. On the other hand, low concentrations of A-PS particles resulted in a reduction of SP-A activity in TT1 cells and a reduction in SP-D activity in A549 cells. These results indicate that nanoparticles can modulate the ability of SP-A and SP-D to combat viral challenges. Furthermore, the nanoparticle concentration, surface chemistry and cell type under investigation are important factors in determining the extent of these modulations.
authors.affiliation: Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Zofi
authors.initials: Z
authors.lastname: McKenzie
authors.affiliation: Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK School of Metallurgy and Materials, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kendall
authors.affiliation: Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Mackay
authors.affiliation: National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
authors.affiliation: Leukocyte Biology, Imperial College London, Royal Brompton Campus, London SW3 6NP, UK.
authors.forename: Cliff
authors.initials: C
authors.lastname: Morgan
authors.affiliation: Leukocyte Biology, Imperial College London, Royal Brompton Campus, London SW3 6NP, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Griffiths
authors.affiliation: Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
authors.forename: Howard W
authors.initials: HW
authors.lastname: Clark
authors.affiliation: Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK j.madsen@southampton.ac.uk.
authors.forename: Jens
authors.initials: J
authors.lastname: Madsen
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D053758:Nanoparticles; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D
keywords: collectin; innate immunity; mucosal; nanoparticles; surface chemistry; surfactant