Lysosomal cysteine proteases are mediators of cell death in macrophages following exposure to amorphous silica nanoparticles. (1st April 2022)

• Record Type: Journal Article
• Authors: Ishaq, Fatima; Sereesongsaeng, Naphannop; Johnston, Michael C.; Scott, Christopher J.; Burden, Roberta E.
• Is Part Of: Chemico-biological interactions. Volume 356(2022)
• Publication Date: 2022-04-01
• Subjects: Nanoparticle -- Silica -- Cell death -- Nanotoxicity -- Lysosome -- Cysteine protease; Baf A1 Bafilomycin A1 -- BMDM bone marrow derived macrophages -- FCS fetal calf serum -- GSDMD gasdermin D -- IL-1β interleukin 1 beta -- LDH lactate dehydrogenase -- NP nanoparticle -- PI propidium iodide -- SiNP silica nanoparticle; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2022.109882
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Increasing use of nanomaterials in everyday products such as cosmetics, medicines and food packaging is of grave concern given the lack of understanding with regards the impact such materials have on biological systems. The aim of this study is to examine cell death induced by cationic amorphous silica nanoparticles and determine the involvement of lysosomal cysteine proteases in this process. We report that multiple forms of cell death including apoptosis and pyroptosis are elicited following exposure to amorphous silica nanoparticles and that lysosomal cysteine proteases are involved in both cell death pathways in macrophages. Interestingly, lysosomal cysteine protease mRNA expression and release into the extracellular environment is induced following exposure to amorphous silica nanoparticles. Previously, the determination of nanoparticle-induced toxicity has focused on cytokine readouts, but the work presented here demonstrates that changes to normal protease biology should also be considered when evaluating the molecular mechanisms by which nanoparticulate matter causes cellular inflammation and death. Highlights: Mechanisms of nanoparticle induced inflammation and death are not fully understood. Protease localization is altered following exposure to silica nanoparticles. Silica nanoparticles induce cell death via apoptosis and pyroptosis. Particle-induced cell death requires protease activity and lysosomal acidification.