title: Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages.
abstract: Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes. Using recombinant forms of the globular regions of human C1q (gC1q) as inhibitors of CNT-mediated classical pathway activation, we show that C1q, the first recognition subcomponent of the classical pathway, binds CNTs via the gC1q domain. Complement opsonisation of CNTs significantly enhances their uptake by U937 cells, with concomitant downregulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines in both U937 cells and human monocytes. We propose that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response.
  
  
  BACKGROUND
  This study highlights the importance of the complement system in response to carbon nanontube administration, suggesting that the ensuing complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response.
authors.affiliation: Neuro Imaging, MIRA Institute, University of Twente, Enschede, The Netherlands; Departments of Biochemistry and Pharmacology, University of Oxford, Oxford, UK; Centre for Infection, Immunity and Disease Mechanisms, Biosciences, Brunel University, London, UK. Electronic address: k.m.pondman@utwente.nl.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Pondman
authors.affiliation: Neuro Imaging, MIRA Institute, University of Twente, Enschede, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Sobik
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Biosciences, Brunel University, London, UK.
authors.forename: Annapurna
authors.initials: A
authors.lastname: Nayak
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Biosciences, Brunel University, London, UK.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Tsolaki
authors.affiliation: Departments of Biochemistry and Pharmacology, University of Oxford, Oxford, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Jäkel
authors.affiliation: Centre Interuniversitaire de Recherche et d'Ingénierie des Matériaux, Institut Carnot Cirimat, Toulouse, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Flahaut
authors.affiliation: Leibniz Institute of Solid State and Materials Research Dresden, IFW-Dresden, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Hampel
authors.affiliation: Neuro Imaging, MIRA Institute, University of Twente, Enschede, The Netherlands.
authors.forename: Bennie
authors.initials: B
authors.lastname: Ten Haken
authors.affiliation: Departments of Biochemistry and Pharmacology, University of Oxford, Oxford, UK; Faculty of Science, Engineering and Computing, Kingston University, Kingston-upon-Thames, UK.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Biosciences, Brunel University, London, UK. Electronic address: uday.kishore@brunel.ac.uk.
authors.forename: Uday
authors.initials: U
authors.lastname: Kishore
mesh_terms: D002460:Cell Line; D003167:Complement Activation / Q000187:drug effects*; D015922:Complement C1q / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D037742:Nanotubes, Carbon / Q000633:toxicity* / Q000648:ultrastructure; D010587:Phagocytosis / Q000187:drug effects*
chemical_list: D016207:Cytokines; D037742:Nanotubes, Carbon; D015922:Complement C1q
keywords: C1q; Carbon nanotubes; Complement; Cytokines; Macrophage