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

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

Published: 19 January 2012



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.


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.


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.

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