Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation
Journal article, 2023
Nanoparticles (NPs) elicit sterile inflammation, but the underlying signaling pathways are poorly understood. Here, we report that human monocytes are particularly vulnerable to amorphous silica NPs, as evidenced by single-cell-based analysis of peripheral blood mononuclear cells using cytometry by time-of-flight (CyToF), while silane modification of the NPs mitigated their toxicity. Using human THP-1 cells as a model, we observed cellular internalization of silica NPs by nanoscale secondary ion mass spectrometry (nanoSIMS) and this was confirmed by transmission electron microscopy. Lipid droplet accumulation was also noted in the exposed cells. Furthermore, time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed specific changes in plasma membrane lipids, including phosphatidylcholine (PC) in silica NP-exposed cells, and subsequent studies suggested that lysophosphatidylcholine (LPC) acts as a cell autonomous signal for inflammasome activation in the absence of priming with a microbial ligand. Moreover, we found that silica NPs elicited NLRP3 inflammasome activation in monocytes, whereas cell death transpired through a non-apoptotic, lipid peroxidation-dependent mechanism. Together, these data further our understanding of the mechanism of sterile inflammation.
cell death
inflammasome
monocyte
mass spectrometry
silica nanoparticles
Author
Govind Gupta
Karolinska Institutet
Swiss Federal Laboratories for Materials Science and Technology (Empa)
Jasreen Kaur
Karolinska Institutet
Kunal Bhattacharya
Karolinska Institutet
Patanjali Res Inst
Benedict J. Chambers
Karolinska Institutet
Arianna Gazzi
University of Padua
Giulia Furesi
Technische Universität Dresden
Martina Rauner
Technische Universität Dresden
Claudia Fuoco
University of Rome Tor Vergata
Marco Orecchioni
La Jolla Inst Immunol, Div Inflammat Biol
Lucia Gemma Delogu
University of Padua
Lars Haag
Karolinska Institutet
Jan Eric Stehr
Linköping University
Aureilien Thomen
University of Gothenburg
Romain Bordes
Chalmers, Chemistry and Chemical Engineering, Applied Chemistry
Per Malmberg
Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry
Gulaim A. Seisenbaeva
Swedish University of Agricultural Sciences (SLU)
Vadim G. Kessler
Swedish University of Agricultural Sciences (SLU)
Michael Persson
Chalmers, Chemistry and Chemical Engineering, Energy and Material
Bengt Fadeel
Karolinska Institutet
ACS Nano
1936-0851 (ISSN) 1936-086X (eISSN)
Vol. 17 e1010515Subject Categories
Immunology in the medical area
Microbiology
DOI
10.1021/acsnano.3c05600
PubMed
37643371