Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation
Artikel i vetenskaplig tidskrift, 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
Författare
Govind Gupta
Karolinska Institutet
Eidgenössische Materialprüfungs- und Forschungsanstalt (Empa)
Jasreen Kaur
Karolinska Institutet
Kunal Bhattacharya
Karolinska Institutet
Patanjali Res Inst
Benedict J. Chambers
Karolinska Institutet
Arianna Gazzi
Università di Padova
Giulia Furesi
Technische Universität Dresden
Martina Rauner
Technische Universität Dresden
Claudia Fuoco
Universita degli Studi di Roma Tor Vergata
Marco Orecchioni
La Jolla Inst Immunol, Div Inflammat Biol
Lucia Gemma Delogu
Università di Padova
Lars Haag
Karolinska Institutet
Jan Eric Stehr
Linköpings universitet
Aureilien Thomen
Göteborgs universitet
Romain Bordes
Chalmers, Kemi och kemiteknik, Tillämpad kemi
Per Malmberg
Chalmers, Kemi och kemiteknik, Kemi och biokemi
Gulaim A. Seisenbaeva
Sveriges lantbruksuniversitet (SLU)
Vadim G. Kessler
Sveriges lantbruksuniversitet (SLU)
Michael Persson
Chalmers, Kemi och kemiteknik, Energi och material
Bengt Fadeel
Karolinska Institutet
ACS Nano
1936-0851 (ISSN) 1936-086X (eISSN)
e1010515Ämneskategorier
Immunologi inom det medicinska området
Mikrobiologi
DOI
10.1021/acsnano.3c05600
PubMed
37643371