Phagocytosis and endocytosis of silver nanoparticles induce interleukin-8 production in human macrophages

Abstract

Phagocytosis or endocytosis by macrophages is critical to the uptake of fine particles, including nanoparticles, in order to initiate toxic effects in cells. Here, our data enhance the understanding of the process of internalization of silver nanoparticles by macrophages. When macrophages were pre-treated with inhibitors to phagocytosis, caveolin-mediated endocytosis, or clathrin-mediated endocytosis, prior to exposure to silver nanoparticles, Interleukin-8 (IL-8) production was inhibited. Although cell death was not reduced, the inflammatory response by macrophages was compromised by phagocytosis and endocytosis inhibitors.

Fig. 1

Cytotoxicity of silver nanoparticles in macrophages. (A) The cytotoxicity in U937 cells were assessed by CCK-8 assay. The LD₅₀ of 5-nm silver nanoparticles was 0.36 µg/mL. (B) Each inhibitors were treaetd 1 hour before exposure to 0.5 µg/mL of 5-nm silver nanoparticles.

Fig. 2

Effects of inhibitors on IL-8 production induced by silver nanoparticles. Each inhibitors were added 1 hour before treatment of nanoparticles. (A) IL-8 in cell culture supernatants were assessed by ELISA 18 hours after exposure to 5-nm silver nanoparticles. (B) Real-time RT-PCR was performent. RNA was perpared from cells treated with 5-nm silver nanoparticles for 2 hours. Chloropromazine was treated at 12.5 µm, nystatin, at 40 µg/mL and cytochalasin D, at 20 µM. ^*p<0.05, ^†p<0.001.