Cytotoxicity of fractured quartz on human macrophages: role of the membranolytic activity of quartz and phagolysosome destabilization.

Abstract

Background The pathogenicity of quartz involves lysosomal alteration in alveolar macrophages. This event triggers the inflammatory cascade that may lead to quartz-induced silicosis and eventually lung cancer. Recently, we showed that synthetic quartz induces membrane lysis in red blood cells and cytotoxic responses in murine alveolar macrophages, only when the atomic order of crystal surfaces is upset by fracturing. Cytotoxicity was not observed when quartz exhibited as-grown, unfractured surfaces. These findings raised questions on the potential impact of quartz surfaces on the phagolysosomal membrane upon internalization of the particles by macrophages.Results To gain insights on the surface-induced cytotoxicity of quartz, as-grown and fractured quartz particles in respirable size, differing only in surface properties related to fracturing, were prepared and physico-chemically characterized. Their effects were compared to a well-known toxic commercial quartz dust. Membranolysis was assessed on red blood cells, and quartz uptake, cell viability, and impact on lysosomes were assessed on human PMA-differentiated THP-1 macrophages. All quartz samples were internalized, but only fractured quartz elicited cytotoxicity and phagolysosomal alterations. These effects were blunted when uptake was suppressed. Membranolysis, but not cytotoxicity, was quenched when fractured quartz surface was masked with serum proteins and incubated with cells.Conclusions Upon internalization, the phagolysosome environment rapidly removes serum proteins from quartz surface, restoring quartz membranolytic activity in the phagolysosomes. Fractured quartz induces cytotoxicity in THP-1 human macrophages by promoting phagolysosomal membrane alterations.