Distinct Pro-Inflammatory Mechanisms Elicited by Short and Long Amosite Asbestos Fibers in Macrophages
Abstract
While exposure to long amphibolic asbestos fibers (L > 10 µm) results in the development of severe diseases including inflammation, fibrosis, and mesothelioma, pathogenic activity associated with short < 5 is less clear. By exposing murine macrophages (SFA) or (LFA) amosite different size surface chemistry, we observed that SFA internalization resulted pyroptotic-related immunogenic cell death (ICD) characterized by release pro-inflammatory damage signal (DAMP) IL-1α after inflammasome activation gasdermin D (GSDMD)-pore formation. In contrast, macrophage responses non-internalizable LFA were tumor necrosis factor alpha (TNF-α) release, caspase-3 -7 activation, apoptosis. effects exclusively from Toll-like receptor 4 (TLR4), a pattern-recognition (PRR) recognized for its ability sense particles, while response was elicited multifactorial ignition system involving collagenous structure (SR-A6 MARCO), reactive oxygen species (ROS) cascade, TLR4. Our findings indicate fiber features play major roles modulating ICD inflammatory pathways. They also suggest are biologically vitro and, therefore, their toxic vivo should not be underestimated.
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