Promotion of allergic immune responses by intranasally-administrated nanosilica particles in mice

With the increase in use of nanomaterials, there is growing concern regarding their potential health risks. However, few studies have assessed the role of the different physical characteristics of nanomaterials in allergic responses. Here, we examined whether intranasally administered silica particles of various sizes have the capacity to promote allergic immune responses in mice. We used nanosilica particles with diameters of 30 or 70 nm (nSP30 or nSP70, respectively), and conventional micro-sized silica particles with diameters of 300 or 1000 nm (nSP300 or mSP1000, respectively). Mice were intranasally exposed to ovalbumin (OVA) plus each silica particle, and the levels of OVA-specific antibodies (Abs) in the plasma were determined. Intranasal exposure to OVA plus smaller nanosilica particles tended to induce a higher level of OVA-specific immunoglobulin (Ig) E, IgG and IgG1 Abs than did exposure to OVA plus larger silica particles. Splenocytes from mice exposed to OVA plus nSP30 secreted higher levels of Th2-type cytokines than mice exposed to OVA alone. Taken together, these results indicate that nanosilica particles can induce allergen-specific Th2-type allergic immune responses in vivo. This study provides the foundations for the establishment of safe and effective forms of nanosilica particles

Effect of amorphous silica nanoparticles on in vitro RANKL-induced osteoclast differentiation in murine macrophages

Amorphous silica nanoparticles (nSP) have been used as a polishing agent and/or as a remineralization promoter for teeth in the oral care field. The present study investigates the effects of nSP on osteoclast differentiation and the relationship between particle size and these effects. Our results revealed that nSP exerted higher cytotoxicity in macrophage cells compared with submicron-sized silica particles. However, tartrate-resistant acid phosphatase (TRAP) activity and the number of osteoclast cells (TRAP-positive multinucleated cells) were not changed by nSP treatment in the presence of receptor activator of nuclear factor κB ligand (RANKL) at doses that did not induce cytotoxicity by silica particles. These results indicated that nSP did not cause differentiation of osteoclasts. Collectively, the results suggested that nanosilica exerts no effect on RANKL-induced osteoclast differentiation of RAW264.7 cells, although a detailed mechanistic examination of the nSP70-mediated cytotoxic effect is needed

Biomonitoring of Urinary Cotinine Concentrations Associated with Plasma Levels of Nicotine Metabolites after Daily Cigarette Smoking in a Male Japanese Population

Human biomonitoring of plasma and urinary levels of nicotine, cotinine, and 3′-hydroxycotinine was conducted after daily cigarette smoking in a population of 92 male Japanese smokers with a mean age of 37 years who had smoked an average of 23 cigarettes per day for 16 years. Members of the population were genotyped for the nicotine-metabolizing enzyme cytochrome P450 2A6 (CYP2A6). The mean levels of nicotine, the levels of its metabolites cotinine and 3′-hydroxycotinine, and the sum of these three levels in subjects one hour after smoking the first cigarette on the sampling day were 20.1, 158, 27.7, and 198 ng/mL in plasma and 846, 1,020, 1,010, and 2,870 ng/mL in urine under daily smoking conditions. Plasma levels of 3′-hydroxycotinine and urinary levels of nicotine and 3′-hydroxycotinine were dependent on the CYP2A6 phenotype group, which was estimated from the CYP2A6 genotypes of the subjects, including those with whole gene deletion. Plasma cotinine levels were significantly correlated with the number of cigarettes smoked on the day before sampling (r = 0.71), the average number of cigarettes smoked daily (r = 0.58), and the Brinkman index (daily cigarettes × years, r = 0.48) under the present conditions. The sum of nicotine, cotinine, and 3′-hydroxycotinine concentrations in plasma showed a similar relationship to that of the plasma cotinine levels. Urinary concentrations of cotinine and the sum of nicotine metabolite concentrations also showed significant correlations with the plasma levels and the previous day’s and average cigarette consumption. The numbers of cigarettes smoked per day by two subjects with self-reported light smoking habits were predicted by measuring the urinary cotinine concentrations and using linear regression equations derived from above-mentioned data. These results indicate that biomonitoring of the urinary cotinine concentration is a good, easy-to-use marker for plasma levels of cotinine and the sum of nicotine metabolites in smokers independent of genetic polymorphism of CYP2A6

Neutrophil Depletion Exacerbates Pregnancy Complications, Including Placental Damage, Induced by Silica Nanoparticles in Mice

Recent advances in nanotechnology have led to the development of nanoparticles with innovative functions in various fields. However, the biological effects of nanoparticles—particularly those on the fetus—need to be investigated in detail, because several previous studies have shown that various nanoparticles induce pregnancy complications in mice. In this regard, our previous findings in mice suggested that the increase in peripheral neutrophil count induced by treatment with silica nanoparticles with a diameter of 70 nm (nSP70) may play a role in the associated pregnancy complications. Therefore, here, we sought to define the role of neutrophils in nSP70-induced pregnancy complications. The peripheral neutrophil count in pregnant BALB/c mice at 24 h after treatment with nSP70 was significantly higher than in saline-treated mice. In addition, maternal body weight, uterine weight, and the number of fetuses in nSP70-treated mice pretreated with anti-antibodies, which deplete neutrophils, were significantly lower than those in nSP70-treated mice pretreated with phosphate-buffered saline or isotype-matched control antibodies. Histology revealed that neutrophil depletion increased nSP70-induced placental damage from the decidua through the spongiotrophoblast layer and narrowed spiral arteries in the placentae. In addition, depletion of neutrophils augmented nSP70-induced cytotoxicity to fetal vessels, which were covered with endothelium. The rate of apoptotic cell death was significantly higher in the placentae of anti-nSP70-treated mice than in those from mice pretreated with isotype-matched control antibodies. Therefore, impairment of placental vessels and apoptotic cell death due to nSP70 exposure is exacerbated in the placentae of nSP70-treated mice pretreated with anti-antibodies. Depletion of neutrophils worsens nSP70-induced pregnancy complications in mice; this exacerbation was due to enhanced impairment of placental vessels and increased apoptotic cell death in maternal placentae. Our results provide basic information regarding the mechanism underlying silica-nanoparticle-induced pregnancy complications