Assessment of changes in autophagic vesicles in human immune cell lines exposed to nano particles

Cell & Bioscience

Andrew Owen¹  David G. Fernig²  Patricia Murray³  Matthew J. Rosseinsky⁴  Michael Barrow⁴  Christopher A. W. David⁵  Neill J. Liptrott⁵  M. Estela del Castillo Busto⁶  Heidi Goenaga-Infante⁶  Susana Cuello-Nuñez⁶ 

[1] Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool, UK;Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool, UK;Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK;Centre for Preclinical Imaging, University of Liverpool, Liverpool, UK;Department of Chemistry, University of Liverpool, Liverpool, UK;Immunocompatibility Group, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK;Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool, UK;National Measurement Institute, LGC Limited, Queens Road, Teddington, TW11 0LY, Middlesex, UK;

关键词: Autophagy;    Nanomaterials;    Nanotoxicology;   

DOI  :  10.1186/s13578-021-00648-8

来源: Springer

【 摘 要 】

BackgroundSafe and rational development of nanomaterials for clinical translation requires the assessment of potential biocompatibility. Autophagy, a critical homeostatic pathway intrinsically linked to cellular health and inflammation, has been shown to be affected by nanomaterials. It is, therefore, important to be able to assess possible interactions of nanomaterials with autophagic processes.ResultsCEM (T cell), Raji (B lymphocyte), and THP-1 (human monocyte) cell lines were subject to treatment with rapamycin and chloroquine, known to affect the autophagic process, in order to evaluate cell line-specific responses. Flow cytometric quantification of a fluorescent autophagic vacuole stain showed that maximum observable effects (105%, 446%, and 149% of negative controls) were achieved at different exposure durations (8, 6, and 24 h for CEM, Raji, and THP-1, respectively). THP-1 was subsequently utilised as a model to assess the autophagic impact of a small library of nanomaterials. Association was observed between hydrodynamic size and autophagic impact (r2 = 0.11, p = 0.004). An ELISA for p62 confirmed the greatest impact by 10 nm silver nanoparticles, abolishing p62, with 50 nm silica and 180 nm polystyrene also lowering p62 to a significant degree (50%, 74%, and 55%, respectively, p < 0.05).ConclusionsThis data further supports the potential for a variety of nanomaterials to interfere with autophagic processes which, in turn, may result in altered cellular function and viability. The association of particle size with impact on autophagy now warrants further investigation.Graphic abstract

【 授权许可】

CC BY