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Part Fibre Toxicol. 2012 Jan 19;9:2. doi: 10.1186/1743-8977-9-2.

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

Author information

  • 1Bioengineering, University of California at Merced, Merced, CA, USA, 5200 North Lake RD, Merced, CA 95343, USA.

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.

PMID:
22260553
[PubMed - indexed for MEDLINE]
PMCID:
PMC3275461
Free PMC Article

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