期刊
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
卷 211, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2021.111900
关键词
Gold nanoparticles; Neutrophil extracellular traps; Scavenger receptor; Extracellular regulated protein kinase; Reactive oxygen species; Reactive oxygen species modulator 1
资金
- National Natural Science Foundation of China [81873955, 81902015]
- Frontier and Applied Basic Research Program of Chongqing [cstc2016jcyjA0105]
- Scientific Innovation Program of Southwest Hospital [SWH2019BJKJ-04]
The study demonstrates a synergistic effect of gold nanoparticles and bacterial lipopolysaccharide in promoting neutrophil extracellular traps release. This synergy is size-dependent, with 10 nm gold nanoparticles being more efficiently taken up by neutrophils compared to larger nanoparticles. Mechanisms involve upregulation of scavenger receptors, activation of ERK and p38 pathways, and the production of reactive oxygen species.
Gold nanoparticles (AuNPs) are extensively utilized in biomedical fields. However, their potential interaction with host cells has not been comprehensively elucidated. In this study, we demonstrated a size-dependent effect of AuNPs to synergize with bacterial lipopolysaccharide (LPS) in promoting neutrophi l extracellular traps (NETs) release in human peripheral neutrophils. Mechanistically, LPS was more efficient to contact with 10 nm AuNPs and promote their uptake in neutrophils compared to 40 and 100 nm AuNPs, leading to a synergistic upregulation of class A scavenger receptor (SRA) which mediated AuNPs uptake and triggered activation of extracellular regulated protein kinase (ERK) and p38. Blocking SRA or inhibiting ERK and p38 activation remarkably abrogated the effect of AuNPs and LPS to induce NETs formation. Further experiments demonstrated that AuNPs and LPS augmented the production of cytosolic reactive oxygen species (ROS) in p38 and ERK dependent manner, through upregulating and activating NADPH oxidase 2 (NOX2). Accordingly, scavenging of ROS or inhibiting the NOX2 dampened NETs release induced by combined AuNPs and LPS treatment. AuNPs and LPS also synergized to upregulate reactive oxygen species modulator 1 (ROMO1) via activating ERK, thereby increasing mitochondrial ROS generation and promoting the release of NETs. In summary, we provide new evidences about the synergy of AuNPs and LPS to augment cellular responses in neutrophils, which implicates the need to consider the amplifying effect by pathogenic stimuli when utilizing nanomaterials in infectious or inflammator y conditions.
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