title: Non-Invasive Imaging Serum Amyloid A Activation through the NF-κB Signal Pathway upon Gold Nanostructure Exposure.
abstract: With the objective of investigating the acute activation of inflammatory cascades upon exposure to gold nanoparticles (GNPs) as well as detailing the mechanisms, a reporter mouse model that allows for non-invasive and longitudinal imaging of hepatic acute-phase serum amyloid A (SAA) activation is constructed. The model is able to visualize SAA activation at the transcriptional stage, with higher sensitivity than serum protein detection by ELISA. GNPs of various sizes (10-80 nm) and geometries are assessed using the reporter mice with results demonstrating that 50 nm nanospheres (GNS50) possess the highest capacity to induce hepatic SAA activation. Detailed analysis uncovers that resident macrophages in the liver are the main origins of these cytokines and that the exposure to GNS50 significantly induces the M1 macrophage phenotype. Moreover, those M1-polarized macrophages, together with the subsequently secreted pro-inflammatory cytokines, exert effects on hepatocytes and then initiate SAA transcription through the NF-κB signal pathway. The results detail the sequential reactions to GNPs among macrophages, inflammatory mediators, and SAA-synthesizing hepatocytes, which shed light on the acute effects of GNPs on the body. In addition, the established in situ and highly sensitive SAA detection system is expected to have vast applications in evaluating NP-induced acute inflammatory reactions.
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.
authors.forename: Shaoduo
authors.initials: S
authors.lastname: Yan
authors.affiliation: WuXi AppTec, Shanghai, 200131, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Ma
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.
authors.forename: Chulin
authors.initials: C
authors.lastname: He
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.|Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Nankai University, Tianjin, 300071, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing, 100850, P. R. China.
authors.forename: Linsheng
authors.initials: L
authors.lastname: Zhan
mesh_terms: D000818:Animals; D006046:Gold / Q000737:chemistry*; D022781:Hepatocytes / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D006046:Gold
keywords: M1-polarized macrophage cells; acute-phase serum amyloid A; bioluminescence imaging; gold nanoparticles; inflammatory response