A mixture of anatase and rutile TiO(2 )nanoparticles induces histamine secretion in mast cells

BACKGROUND: Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca(2+ )signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO(2 )NPs), a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain. RESULTS: TiO(2 )NP exposure increased both histamine secretion and cytosolic Ca(2+ )concentration ([Ca(2+)](C)) in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca(2+ )levels resulted primarily from an extracellular Ca(2+ )influx via membrane L-type Ca(2+ )channels. Unspecific Ca(2+ )entry via TiO(2 )NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO(2 )NPs also contributed to cytosolic Ca(2+ )signaling. The PLC-IP(3)-IP(3 )receptor pathways and endoplasmic reticulum (ER) were responsible for the sustained elevation of [Ca(2+)](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 TiO(2 )NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.