Effect of Silica Particle Size on Macrophage Inflammatory Responses

Toshimasa Kusaka,Emi Furusawa,Kouetsu Ogasawara,Mai Ishimiya,Kyohei Nakamura,Masafumi Nakayama,Hiroyasu Nakano

doi:10.1371/journal.pone.0092634

Abstract

Amorphous silica particles, such as nanoparticles (<100 nm diameter particles), are used in a wide variety of products, including pharmaceuticals, paints, cosmetics, and food. Nevertheless, the immunotoxicity of these particles and the relationship between silica particle size and pro-inflammatory activity are not fully understood. In this study, we addressed the relationship between the size of amorphous silica (particle dose, diameter, number, and surface area) and the inflammatory activity (macrophage phagocytosis, inflammasome activation, IL-1β secretion, cell death and lung inflammation). Irrespective of diameter size, silica particles were efficiently internalized by mouse bone marrow-derived macrophages via an actin cytoskeleton-dependent pathway, and induced caspase-1, but not caspase-11, activation. Of note, 30 nm-1000 nm diameter silica particles induced lysosomal destabilization, cell death, and IL-1β secretion at markedly higher levels than did 3000 nm-10000 nm silica particles. Consistent with in vitro results, intra-tracheal administration of 30 nm silica particles into mice caused more severe lung inflammation than that of 3000 nm silica particles, as assessed by measurement of pro-inflammatory cytokines and neutrophil infiltration in bronchoalveolar lavage fluid of mice, and by the micro-computed tomography analysis. Taken together, these results suggest that silica particle size impacts immune responses, with submicron amorphous silica particles inducing higher inflammatory responses than silica particles over 1000 nm in size, which is ascribed not only to their ability to induce caspase-1 activation but also to their cytotoxicity.

Highlights

Inhalation of silica causes silicosis, which is one of the most prevalent occupational diseases worldwide [1,2]
At around 0.1 mg/ml, 30 nm silica particles induced the higher amounts of IL-1b secretion from Bone marrow-derived macrophages (BMDMs) than did the larger size of silica particles, at higher concentrations of 1 mg/mL, 100–1000 nm silica particles induced more IL-1b than did 30 nm silica particles (Figure 1A)
Regarding the IL-1b secretion activity per particle number (Figure 1B) or per particle surface area (Figure 1C), 300 nm and 1000 nm silica were found to be stronger than 30 nm silica particles

Summary

Introduction

Inhalation of silica ( known as silicon dioxide) causes silicosis, which is one of the most prevalent occupational diseases worldwide [1,2]. Silicosis is irreversible and the disease progresses even when exposure to silica stops [1]. Silica is divided into two forms, crystalline and amorphous. These two forms are composed of the same molecular element (SiO2), their physical properties are different. Several recent studies have shown that both amorphous silica and crystalline silica are toxic in vitro and in vivo [4,5,6]. The toxicity of silica nanoparticles continues to be a matter of debate. A detailed study investigating the relationship between silica particle size and toxicity is required

Methods

Results

Conclusion