Imperial College London
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DrHarryWhitwell

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Lecturer in Proteomics and Integrative Data Analysis Proteom
 
 
 
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Location

 

312Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{McKenzie:2015:10.3109/17435390.2014.992487,
author = {McKenzie, Z and Kendall, M and Mackay, R-M and Whitwell, H and Elgy, C and Ding, P and Mahajan, S and Morgan, C and Griffiths, M and Clark, H and Madsen, J},
doi = {10.3109/17435390.2014.992487},
journal = {Nanotoxicology},
pages = {952--962},
title = {Surfactant protein A (SP-A) inhibits agglomeration and macrophage uptake of toxic amine modified nanoparticles},
url = {http://dx.doi.org/10.3109/17435390.2014.992487},
volume = {9},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The lung provides the main route for nanomaterial exposure. Surfactant protein A (SP-A) is an important respiratory innate immune molecule with the ability to bind or opsonise pathogens to enhance phagocytic removal from the airways. We hypothesised that SP-A, like surfactant protein D, may interact with inhaled nanoparticulates, and that this interaction will be affected by nanoparticle (NP) surface characteristics. In this study, we characterise the interaction of SP-A with unmodified (U-PS) and amine-modified (A-PS) polystyrene particles of varying size and zeta potential using dynamic light scatter analysis. SP-A associated with both 100 nm U-PS and A-PS in a calcium-independent manner. SP-A induced significant calcium-dependent agglomeration of 100 nm U-PS NPs but resulted in calcium-independent inhibition of A-PS self agglomeration. SP-A enhanced uptake of 100 nm U-PS into macrophage-like RAW264.7 cells in a dose-dependent manner but in contrast inhibited A-PS uptake. Reduced association of A-PS particles in RAW264.7 cells following pre-incubation of SP-A was also observed with coherent anti-Stokes Raman spectroscopy. Consistent with these findings, alveolar macrophages (AMs) from SP-A−/− mice were more efficient at uptake of 100 nm A-PS compared with wild type C57Bl/6 macrophages. No difference in uptake was observed with 500 nm U-PS or A-PS particles. Pre-incubation with SP-A resulted in a significant decrease in uptake of 100 nm A-PS in macrophages isolated from both groups of mice. In contrast, increased uptake by AMs of U-PS was observed after pre-incubation with SP-A. Thus we have demonstrated that SP-A promotes uptake of non-toxic U-PS particles but inhibits the clearance of potentially toxic A-PS particles by blocking uptake into macrophages.
AU  - McKenzie,Z
AU  - Kendall,M
AU  - Mackay,R-M
AU  - Whitwell,H
AU  - Elgy,C
AU  - Ding,P
AU  - Mahajan,S
AU  - Morgan,C
AU  - Griffiths,M
AU  - Clark,H
AU  - Madsen,J
DO  - 10.3109/17435390.2014.992487
EP  - 962
PY  - 2015///
SN  - 1743-5404
SP  - 952
TI  - Surfactant protein A (SP-A) inhibits agglomeration and macrophage uptake of toxic amine modified nanoparticles
T2  - Nanotoxicology
UR  - http://dx.doi.org/10.3109/17435390.2014.992487
UR  - http://hdl.handle.net/10044/1/41309
VL  - 9
ER  -
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