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.
Highlights
The rapid growth in the nanotechnology industry has led to concerns regarding the potential health implications of nanomaterial exposures
We have previously shown that Surfactant protein A (SP-A) and SP-D interact with nanoparticles and that these interactions can alter particle agglomeration and uptake by phagocytes such as macrophages
The effect of 100 nm cationic amine modified polystyrene (A-PS) and anionic unmodified polystyrene (U-PS) nanoparticles on the ability of SP-A/ SP-D to neutralize influenza A virus (IAV) infection in vitro was examined in TT1, A549 and differentiated THP-1 cell lines
Summary
The rapid growth in the nanotechnology industry has led to concerns regarding the potential health implications of nanomaterial exposures. Pre-natal exposure to PM2.5 has been shown to increase the incidence of recurrent pneumonia and acute bronchitis in children in a concentration dependent manner. Pre-exposure to DE and DEP has been shown to increase respiratory syncytial virus (RSV) infection and viral induced lung inflammation in mice in vivo. The evidence surrounding the enhanced susceptibility to respiratory infections following particulate exposure relates to ambient particulate matter rather than engineered nanoparticles. The SP-A and SP-D interaction with magnetite particles possessing different polymer coatings has been investigated These studies have shown that both SP-A and SP-D enhance the uptake by macrophages of magnetite particles with hydrophobic and hydrophilic surface coatings. THP-1 cells were kindly provided by Liku Tezera and were grown in RPMI1640 medium containing 10% heat inactivated FBS (PAA, UK) and 100 units ml penicillin and 100 mg ml streptomycin. NP inhibition of infection inhibition of progeny virions inhibition of SP-A/D binding to IAV
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