Modulation of macrophage activities in proliferation, lysosome, and phagosome by the nonspecific immunostimulator, mica

Abstract

It was reported that the aluminosilicate materialmica activated macrophages and showed its immunostimulating effects. However, the mechanisms by which it exerts these effects are unclear. To address this, we evaluated the effects of mica fine particles (MFP, 804.1 ± 0.02 nm) on the murinemacrophage cell line, RAW 264.7. Specifically, RAW 264.7 cells were treated with 100 and 500 μg/mL MFP and their proliferative response was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Changes in global gene expression upon MFP treatment for 12 and 48 h were also determined using microarrays. Following theMFP treatment, RAW 264.7 cells showed a low level of proliferation compared to nontreated cells (p < 0.01). There was a change in an expression level of 1,128 genes after 48 h treatment. Specifically, genes associated with the cell cycle, DNA replication, and pyrimidine and purinemetabolisms, were down-regulated in cells treated with MFP, which resulted in reduction of cell proliferation. MFP treatment also up-regulated genes associated with lysosome and phagosome function, which are both required for macrophage activities. We speculate that activation of macrophages by mica is in part derived from up-regulation of these pathways.