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 e1010515

Subject Categories

Immunology in the medical area

Microbiology

DOI

10.1021/acsnano.3c05600

PubMed

37643371

More information

Latest update

7/17/2024