Immunotoxicology of high aspect ratio nanomaterials

  • Author / Creator
    Ede, James D
  • Immune models have been highlighted in nanotoxicology for their applicability in understanding the effects of both accidental exposure (e.g. environmental exposure) and therapeutic exposure (e.g. targeted drug delivery) to nanomaterials (NMs). The experiments presented here examine the immunotoxicology of three high aspect ratio nanomaterials (HARNs), rosette nanotubes (RNTs), carbon nanotubes (CNTs) and cellulose nanocrystals (CNCs), using in vitro teleost and mammalian models. The data presented in this thesis adds to reports that HARNs are not necessarily associated with high levels of cytotoxicity and declines in viability in mammalian models occur at concentrations of HARNs that are above those anticipated for either environmental or therapeutic applications. I observe differential cytotoxicity for all three HARNs examined and the toxicity of each material is altered with differential surface functionalization. In addition, several HARNs interfered with receptor-mediated immune effector responses in vitro at sub-lethal levels of exposure and these effects differed between the type of HARNs and their functionalization. Sub-lethal exposure to RNTs enhanced, while sub-lethal CNT exposure reduced, IgE-FcεRI-mediated degranulation. I propose a mechanism for the observed immunomodulation of receptor-mediated effector function following HARN exposure, suggesting that the presence of NMs interferes with receptor engagement of their respective ligand.

    The work presented here is also one of the first to examine the effect of NM exposure on fish lymphoid cells. Exposure of fish lymphocytes to HARNs resulted in significant declines in viability at concentrations that were an order of magnitude lower than mammalian leukocytes. In addition, immunomodulation of teleost receptor-mediated effector responses was observed following HARN exposure. RNT and CNT exposure significantly reduced Ictalurus punctatus Leukocyte Immune Type Receptor (IpLITR)-mediated phagocytosis at sub-lethal levels of exposure and was functionalization dependent. The availability of several in vitro leukocyte cell lines and the use of IpLITR as a model to examine the sub-lethal effect of NM exposure on immune cell effector function make channel catfish an ideal model for future aquatic nanotoxicity testing.

  • Subjects / Keywords
  • Graduation date
    Fall 2015
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.