title: Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, UK; Neuro Imaging, MIRA Institute, University of Twente, Enschede, the Netherlands.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Pondman
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, UK.
authors.forename: Lina
authors.initials: L
authors.lastname: Pednekar
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, UK.
authors.forename: Basudev
authors.initials: B
authors.lastname: Paudyal
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, UK.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Tsolaki
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, UK.
authors.forename: Lubna
authors.initials: L
authors.lastname: Kouser
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Haseeb A
authors.initials: HA
authors.lastname: Khan
authors.affiliation: Allergy and Clinical Immunology, National Heart and lung Institute, Imperial College London, London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Shamji
authors.affiliation: Neuro Imaging, MIRA Institute, University of Twente, Enschede, the Netherlands.
authors.forename: Bennie
authors.initials: B
authors.lastname: Ten Haken
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, UK.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Stenbeck
authors.affiliation: Department of Pharmacology, University of Oxford, Oxford, UK; Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Department of Life Sciences, College of Health and Life Sciences, 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; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003167:Complement Activation; D015922:Complement C1q / Q000276:immunology*; D017242:Complement Factor H / Q000276:immunology*; D003165:Complement System Proteins; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology*; D037742:Nanotubes, Carbon / Q000009:adverse effects* / Q000737:chemistry / Q000648:ultrastructure; D010587:Phagocytosis
chemical_list: D020099:Coated Materials, Biocompatible; D037742:Nanotubes, Carbon; D015922:Complement C1q; D017242:Complement Factor H; D003165:Complement System Proteins
keywords: C1q; Carbon nanotubes; Complement; Factor H; Immune system; Innate immunity; Nanotherapeutics