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Distinct Pro-Inflammatory Mechanisms Elicited by Short and Long Amosite Asbestos Fibers in Macrophages

Riccardo Leinardi1, Jasmine Rita Petriglieri2,3, Amandine Pochet1

  • 1Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institute de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.

International Journal of Molecular Sciences
|October 28, 2023
PubMed

Insights

Short asbestos fibers (SFA) trigger pyroptosis via Toll-like receptor 4 (TLR4), causing immunogenic cell death. Long asbestos fibers (LFA) induce apoptosis through a different pathway, highlighting fiber size

Area of Science:

  • Toxicology
  • Immunology
  • Materials Science

Background:

  • Long asbestos fibers (>10 µm) are known to cause severe diseases like mesothelioma.
  • The pathogenic effects of short asbestos fibers (<5 µm) are less understood, particularly in immune cells.

Purpose of the Study:

  • To investigate the differential effects of short (SFA) and long (LFA) amosite asbestos fibers on murine macrophages.
  • To elucidate the molecular mechanisms underlying macrophage responses to asbestos fibers of varying sizes.

Main Methods:

  • Murine macrophages were exposed to SFA and LFA with distinct size and surface chemistry.
  • Cell death pathways (pyroptosis, apoptosis) and inflammatory signaling (cytokine release, receptor activation) were analyzed.

Main Results:

  • SFA induced pyroptosis-related immunogenic cell death (ICD) via inflammasome activation, gasdermin D (GSDMD) pore formation, and IL-1α release, exclusively through Toll-like receptor 4 (TLR4).
  • LFA exposure led to TNF-α release, caspase-3/-7 activation, and apoptosis, involving MARCO, ROS, and TLR4.
  • Asbestos fiber size and surface properties significantly modulate macrophage responses and inflammatory pathways.

Conclusions:

  • Short asbestos fibers are biologically reactive in vitro, inducing ICD through TLR4-mediated pyroptosis.
  • The distinct mechanisms triggered by SFA and LFA underscore the importance of fiber characteristics in asbestos-induced toxicity.
  • The inflammatory and toxic potential of short asbestos fibers in vivo warrants further investigation and should not be underestimated.
Keywords:
IL-1αTLR4TNF-αamosite asbestosapoptosisgasdermin Dimmunogenic cell deathinflammationmacrophagespyroptosis

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