Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes

Kirsten M. Pondman, Lina Pednekar, Basudev Paudyal, Anthony G. Tsolaki, Lubna Kouser, Haseeb A. Khan, Mohamed H. Shamji, Bennie ten Haken, Gudrun Stenbeck, Robert B. Sim, Uday Kishore*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)
2 Downloads (Pure)

Abstract

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. From the Clinical Editor: Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.

Original languageEnglish
Pages (from-to)2109-2118
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume11
Issue number8
DOIs
Publication statusPublished - 1 Nov 2015

Keywords

  • C1q
  • Carbon nanotubes
  • Complement
  • Factor H
  • Immune system
  • Innate immunity
  • Nanotherapeutics

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