Nicotine alters mucin rheological properties.

Tobacco smoke exposure, the major cause of chronic obstructive pulmonary disease (COPD), instigates a dysfunctional clearance of thick obstructive mucus. However, the mechanism underlying the formation of abnormally viscous mucus remains elusive. We investigated whether nicotine can directly alter the rheological properties of mucin by examining its physicochemical interactions with human airway mucin gels secreted from A549 lung epithelial cells. Swelling kinetics and multiple particle tracking were utilized to assess mucin gel viscosity change when exposed to nicotine. Herein we show that nicotine (≤50 nM) significantly hindered postexocytotic swelling and hydration of released mucins, leading to higher viscosity, possibly by electrostatic and hydrophobic interactions. Moreover, the close association of nicotine and mucins allows airway mucus to function as a reservoir for prolonged nicotine release, leading to correlated pathogenic effects. Our results provide a novel explanation for the maltransport of poorly hydrated mucus in smokers. More importantly, this study further indicates that even low-concentration nicotine can profoundly increase mucus viscosity and thus highlights the health risks of secondhand smoke exposure.

A mixture of anatase and rutile TiO2 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 Ca²âº 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 Ca²âº concentration ([Ca²âº]C) in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca²âº levels resulted primarily from an extracellular Ca²âº influx via membrane L-type Ca²âº channels. Unspecific Ca²âº 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 Ca²âº signaling. The PLC-IP3-IP3 receptor pathways and endoplasmic reticulum (ER) were responsible for the sustained elevation of [Ca²âº]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.