Journal of Nanomedicine & Nanotechnology

Abstract

Neutrophilia Due to Silica Nanoparticles Induces Release of Double- Stranded DNA

Kazuma Higashisaka, Akiyoshi Kunieda, Yuki Iwahara, Kota Tanaka, Kazuya Nagano, Yohei Mukai, Haruhiko Kamada, Shin-ichi Tsunoda, Yasuo Yoshioka and Yasuo Tsutsumi

Various types of nanomaterials have been developed for consumer and industrial applications, and the safety of such materials is the subject of considerable research around the world. Several studies have reported the inflammatory effects of nanomaterials, but the details of the involvement of neutrophils, the first leukocytes to be recruited to inflammation sites, in nanomaterial-induced inflammation are poorly understood. Here, we examined neutrophil activation in mice treated with silica particles. Twenty-four hours after treatment, the proportion of neutrophils in peripheral blood of mice injected with 70-nm-diameter silica nanoparticles (nSP70) was significantly higher than in saline-treated mice, whereas treatment with silica particles with diameters of 300 or 1000 nm did not result in any significant change in neutrophil proportion. In addition, higher plasma concentrations of myeloperoxidase were observed only in the nSP70-treated mice, and treatment with nSP70 surface-modified with amino groups did not elevate the proportion of neutrophils. Moreover, mice treated with antibodies to granulocyte colony-stimulating factor (G-CSF) exhibited a significant decrease in nSP70-induced neutrophilia relative to untreated mice, suggesting that nSP70- induced neutrophilia resulted from G-CSF production induced by nSP70. In addition, we demonstrate that nSP70- induced neutrophilia contributed to elevation of plasma concentrations of double-stranded DNA. Our results indicate that the nSP70-induced increase in the proportion of neutrophils depended on G-CSF elevation and that nSP70 may have induced the formation of neutrophil extracellular traps. Our results provide basic information about the association of neutrophil activation with silica nanoparticle–induced biological effects.