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Surfactant protein A (SP-A) inhibits agglomeration and macrophage uptake of toxic amine modified nanoparticles.

Surfactant protein A (SP-A) inhibits agglomeration and macrophage uptake of toxic amine modified nanoparticles.
Surfactant protein A (SP-A) inhibits agglomeration and macrophage uptake of toxic amine modified nanoparticles.
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.
collectin, mucosal, nanoparticles, surface chemistry, surfactant
1743-5390
952-962
Mckenzie, Zofi
b4f47115-f00c-4f6c-8e54-030da0da0736
Kendall, Michaela
ec95f244-5349-4521-a60f-4a60648f6de3
Mackay, Rose-Marie
19cf1b92-c65d-4baa-a165-ab630bf77ec3
Whitwell, Harry
94b6f20c-7924-4b33-8973-010616da9bcf
Elgy, Christine
9dc5e317-7809-46ba-9e70-75bcc9700ff5
Ding, Ping
e39793b6-1e6c-488c-b252-5c1c64c224fc
Mahajan, Sumeet
b131f40a-479e-4432-b662-19d60d4069e9
Morgan, Cliff
74b0ee12-7045-44d3-bfe7-1118bbdfe463
Griffiths, Mark
ff46d26f-2a28-4a6a-b189-d838abfcf8f7
Clark, Howard
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Madsen, Jens
b5d8ae35-00ac-4d19-930e-d8ddec497359
Mckenzie, Zofi
b4f47115-f00c-4f6c-8e54-030da0da0736
Kendall, Michaela
ec95f244-5349-4521-a60f-4a60648f6de3
Mackay, Rose-Marie
19cf1b92-c65d-4baa-a165-ab630bf77ec3
Whitwell, Harry
94b6f20c-7924-4b33-8973-010616da9bcf
Elgy, Christine
9dc5e317-7809-46ba-9e70-75bcc9700ff5
Ding, Ping
e39793b6-1e6c-488c-b252-5c1c64c224fc
Mahajan, Sumeet
b131f40a-479e-4432-b662-19d60d4069e9
Morgan, Cliff
74b0ee12-7045-44d3-bfe7-1118bbdfe463
Griffiths, Mark
ff46d26f-2a28-4a6a-b189-d838abfcf8f7
Clark, Howard
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Madsen, Jens
b5d8ae35-00ac-4d19-930e-d8ddec497359

Mckenzie, Zofi, Kendall, Michaela, Mackay, Rose-Marie, Whitwell, Harry, Elgy, Christine, Ding, Ping, Mahajan, Sumeet, Morgan, Cliff, Griffiths, Mark, Clark, Howard and Madsen, Jens (2015) Surfactant protein A (SP-A) inhibits agglomeration and macrophage uptake of toxic amine modified nanoparticles. Nanotoxicology, 9 (8), 952-962. (doi:10.3109/17435390.2014.992487). (PMID:25676620)

Record type: Article

Abstract

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.

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Accepted/In Press date: 24 November 2014
e-pub ahead of print date: 13 February 2015
Published date: 13 February 2015
Keywords: collectin, mucosal, nanoparticles, surface chemistry, surfactant
Organisations: Institute for Life Sciences, Chemical Biology Group

Identifiers

Local EPrints ID: 375064
URI: https://eprints.soton.ac.uk/id/eprint/375064
ISSN: 1743-5390
PURE UUID: 8bf2dc3e-9778-4b6b-b548-bad34cae4323
ORCID for Rose-Marie Mackay: ORCID iD orcid.org/0000-0002-9493-9654
ORCID for Sumeet Mahajan: ORCID iD orcid.org/0000-0001-8923-6666
ORCID for Jens Madsen: ORCID iD orcid.org/0000-0003-1664-7645

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Date deposited: 11 Mar 2015 12:21
Last modified: 06 Jun 2018 12:38

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