Phagocytized Silica Particles Cause IL-1β Release and Cell Death in Peritoneal Macrophages

Abstract

Objective: When cells are incubated with various particles in phagocytosis experiment, the cells include two populations. One is the population which engulfed the particles; the other is the population which did not engulf them. We separated both populations by use of a cell sorter and evaluated the cell death of the population which engulfed the particles to clarify the cytotoxic effect by the phagocytized particles in this study. Methods and Results: Thioglycollate-elicited peritoneal macrophages engulfed 100 nm and 1000 nm of non-crystalline silica and polystyrene particles. Phagocytosis of these particles increased depending on the quantity of added particles. The treatment of the cells with 1000 nm silica particles induced release of lactate dehydrogenase (LDH) and production of interleukin-1β (IL-1β). On the other hand, 100 nm silica particles did not increase the LDH release and the IL-1β production. Polystyrene particles also did not have cytotoxic and inflammatory effects. To elucidate the relation of phagocytosis and cytotoxicity, the cells incubated with 1000 nm silica particles were divided into non-phagocytic and phagocytic population by use of a cell sorter. As most of dead cells stained by propidium iodide were observed in the phagocytic cells population, the phagocytosis of 1000 nm silica particle was associated with cell damage directly. The silica-induced cell death was not accompanied with the externalization of phosphatidylserine in the plasma membrane. Conclusions: These results indicated the following things: (1) The engulfment of certain size of the silica particles induced cell death in the macrophages, (2) The cell death was not typical apoptosis and (3) The cell death was accompanied with the activation of inflammasome.