Catastrophic Inflammatory Death of Monocytes and Macrophages by Overtaking of A Critical Dose of Endocytosed Synthetic Amorphous Silica Nanoparticles/Serum Protein Complexes

AIMS: We tested whether phagocytic monocytes/macrophages are more susceptible than nonphagocytes to nanoparticle (NP) toxicity. MATERIALS & METHODS: We compared in vitro cell death and proinflammatory cytokine production in human monocytes, macrophages, lymphocytes and HeLa cells due to synthetic amorphous silica (SiO2)-NPs in different serum concentrations and correlated them with cellular uptake and distribution. RESULTS: Phagocytes were approximately ten-times more sensitive than nonphagocytes to SiO2-NPs and more effectively endocytosed SiO2-NP-serum protein nanoagglomerates, so determining their accumulation in acidic endocytic compartments well beyond a critical/cytotoxic threshold. Monocyte/macrophage death was paralleled by cytokine secretion. CONCLUSION: The physiological specialization of monocytes/macrophages to effectively capture NPs may expose them to the risk of catastrophic inflammatory death upon saturation of their maximal storage capacity.