Rosette Nanotubes Alter IgE-Mediated Degranulation in the Rat Basophilic Leukemia (RBL)-2H3 Cell Line

Toxicol Sci. 2015 Nov;148(1):108-20. doi: 10.1093/toxsci/kfv166. Epub 2015 Jul 29.

Abstract

In this study, the effects of rosette nanotube (RNT) exposure on immune cell viability and function were investigated in vitro using the rat basophilic leukemia (RBL)-2H3 cell line. RBL-2H3 viability was decreased in a dose- and time-dependent manner after lysine-functionalized RNT (K-RNT) exposure. In addition, K-RNTs had a significant effect on RBL-2H3 degranulation. When K-RNT exposure was concurrent with IgE sensitization, 50 and 100 mg l(-1) K-RNTs elicited a heightened degranulatory response compared with IgE alone. Exposure to 50 and 100 mg l(-1) K-RNTs also caused degranulation in RBL-2H3 cells not sensitized with IgE (0 ng ml(-1) IgE). Furthermore, in cells preexposed to K-RNTs for 2 h and subsequently washed, sensitized, and stimulated with IgE, a potentiated degranulatory response was observed. Using confocal laser scanning microscopy and a fluorescein isothiocyanate (FITC)-functionalized RNT construct (termed FITC(1)/TBL(19)-RNT), we demonstrated a strong and direct affiliation between RNTs and RBL-2H3 cell membranes. We also demonstrated cellular internalization of RNTs after 2 h of exposure. Together, these data demonstrate that RNTs may affiliate with the cellular membrane of RBL-2H3 cells and can be internalized. These interactions can affect viability and alter the ability of these cells to elicit IgE-FcεR mediated degranulation.

Keywords: degranulation; inflammation; nanotoxicology; rosette nanotubes; self-assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption, Physiological
  • Animals
  • Basophil Degranulation Test
  • Basophils / cytology
  • Basophils / drug effects*
  • Basophils / immunology
  • Biocompatible Materials / adverse effects
  • Biocompatible Materials / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Carriers
  • Fluorescein-5-isothiocyanate / chemistry
  • Fluorescent Dyes / chemistry
  • Genes, Reporter / drug effects
  • HEK293 Cells
  • Humans
  • Hydrogen Bonding
  • Immunoglobulin E / metabolism*
  • Lysine / chemistry
  • MAP Kinase Signaling System / drug effects
  • Microscopy, Confocal
  • Nanotubes / chemistry
  • Nanotubes / toxicity*
  • Rats
  • Surface Properties
  • Up-Regulation / drug effects*

Substances

  • Biocompatible Materials
  • Drug Carriers
  • Fluorescent Dyes
  • Immunoglobulin E
  • Fluorescein-5-isothiocyanate
  • Lysine