摘要
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. © 2012 Chen et al; licensee BioMed Central Ltd.