Email updates

Keep up to date with the latest news and content from P&FT and BioMed Central.

Open Access Research

A mixture of anatase and rutile TiO2 nanoparticles induces histamine secretion in mast cells

Eric Y Chen, Maria Garnica, Yung-Chen Wang, Alexander J Mintz, Chi-Shuo Chen and Wei-Chun Chin*

Author Affiliations

Bioengineering, University of California at Merced, Merced, CA, USA. 5200 North Lake RD, Merced, CA 95343, USA

For all author emails, please log on.

Particle and Fibre Toxicology 2012, 9:2  doi:10.1186/1743-8977-9-2

Published: 19 January 2012

Abstract

Background

Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca2+ signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO2 NPs), a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain.

Results

TiO2 NP exposure increased both histamine secretion and cytosolic Ca2+ concentration ([Ca2+]C) in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca2+ levels resulted primarily from an extracellular Ca2+ influx via membrane L-type Ca2+ channels. Unspecific Ca2+ entry via TiO2 NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO2 NPs also contributed to cytosolic Ca2+ signaling. The PLC-IP3-IP3 receptor pathways and endoplasmic reticulum (ER) were responsible for the sustained elevation of [Ca2+]C and histamine secretion.

Conclusion

Our data suggests that systemic circulation of NPs may prompt histamine release at different locales causing abnormal inflammatory diseases. This study provides a novel mechanistic link between environmental TiO2 NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.

Keywords:
TiO2 nanoparticles; mast cell; histamine release; Ca2+ signaling