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Pulmonary surfactant protein SP-D opsonises carbon nanotubes and augments their phagocytosis and subsequent pro-inflammatory immune response.

Authors
  • Pondman, Kirsten M1
  • Paudyal, Basudev2
  • Sim, Robert B3
  • Kaur, Anuvinder4
  • Kouser, Lubna4
  • Tsolaki, Anthony G4
  • Jones, Lucy A5
  • Salvador-Morales, Carolina6
  • Khan, Haseeb A7
  • Ten Haken, Bennie8
  • Stenbeck, Gudrun4
  • Kishore, Uday4
  • 1 Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK. [email protected] [email protected] and Neuro Imaging, MIRA Institute, University of Twente, Enschede, The Netherlands. , (Netherlands)
  • 2 Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK. [email protected] [email protected] and Faculty of Science, Engineering and Computing, Kingston University Penrhyn Road, Kingston upon Thames, Surrey, KT1 2EE, UK.
  • 3 Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK.
  • 4 Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK. [email protected] [email protected]
  • 5 Faculty of Science, Engineering and Computing, Kingston University Penrhyn Road, Kingston upon Thames, Surrey, KT1 2EE, UK.
  • 6 Bioengineering Department and Krasnow Institute for Advanced Study, George Mason University, Fairfax, 22030 Virginia, USA.
  • 7 Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. , (Saudi Arabia)
  • 8 Neuro Imaging, MIRA Institute, University of Twente, Enschede, The Netherlands. , (Netherlands)
Type
Published Article
Journal
Nanoscale
Publisher
The Royal Society of Chemistry
Publication Date
Jan 19, 2017
Volume
9
Issue
3
Pages
1097–1109
Identifiers
DOI: 10.1039/c6nr08807d
PMID: 27991644
Source
Medline
Language
English
License
Unknown

Abstract

Carbon nanotubes (CNTs) are increasingly being developed for use in biomedical applications, including drug delivery. One of the most promising applications under evaluation is in treating pulmonary diseases such as tuberculosis. Once inhaled or administered, the nanoparticles are likely to be recognised by innate immune molecules in the lungs such as hydrophilic pulmonary surfactant proteins. Here, we set out to examine the interaction between surfactant protein D (SP-D), a key lung pattern recognition molecule and CNTs, and possible downstream effects on the immune response via macrophages. We show here that a recombinant form of human SP-D (rhSP-D) bound to oxidised and carboxymethyl cellulose (CMC) coated CNTs via its C-type lectin domain and enhanced phagocytosis by U937 and THP-1 macrophages/monocytic cell lines, together with an increased pro-inflammatory response, suggesting that sequestration of SP-D by CNTs in the lungs can trigger an unwanted and damaging immune response. We also observed that functionalised CNTs, opsonised with rhSP-D, continued to activate complement via the classical pathway, suggesting that C1q, which is the recognition sub-component of the classical pathway, and SP-D have distinct pattern recognition sites on the CNTs. Consistent with our earlier reports, complement deposition on the rhSP-D opsonised CNTs led to dampening of the pro-inflammatory immune response by THP-1 macrophages, as evident from qPCR, cytokine array and NF-κB nuclear translocation analyses. This study highlights the importance of understanding the interplay between innate immune humoral factors including complement in devising nanoparticle based drug delivery strategies.

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