Crystalline Silica Particles Mediated Lung Injury

Dutta, Debamitra; Moudgil, Brij M.

doi:10.14356/kona.2007009

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…In fact, both particles and dead cells can stimulate macrophages to produce inflammatory mediators [7,8,12,15]. Therefore, a repeating cycle of particle ingestion, inflammatory cell death, and the release of particles back into the environment for reingestion by other cells is thought to drive such pathology [16].…”

Section: Introductionmentioning

confidence: 99%

Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation

Orlowski

Sharma

Colbert

et al. 2017

Journal of Leukocyte Biology

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Sterile particles cause several chronic, inflammatory diseases, characterized by repeating cycles of particle phagocytosis and inflammatory cell death. Recent studies have proposed that these processes are driven by the NLRP3 inflammasome, a platform activated by phagocytosed particles, which controls both caspase-1-dependent cell death (pyroptosis) and mature IL-1β secretion. After phagocytosis, particles can disrupt lysosomes, and inhibitor studies have suggested that the resulting release of a lysosomal protease-cathepsin B-into the cytosol somehow activates NLRP3. However, using primary murine macrophages, we found that particle-induced cell death occurs independent of NLRP3/caspase-1 and depends instead on multiple, redundant cathepsins. In contrast, nigericin, a soluble activator of NLRP3 inflammasomes, induced cell death that was dependent on the NLRP3. Interestingly, nigericin-induced cell death depended partly on a single cathepsin, cathepsin X. By inhibiting or silencing multiple cathepsins in macrophages, several key proinflammatory events induced by sterile particles are blocked, including cell death, pro-IL-1β production, and IL-1β secretion. These data suggest that cathepsins might be potential therapeutic targets in particulate-mediated inflammatory disease. In support of this concept, we find that a broad-spectrum cathepsin inhibitor can suppress particle-induced IL-1-dependent peritonitis.

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Section: Introductionmentioning

confidence: 99%

Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation

Orlowski

Sharma

Colbert

et al. 2017

Journal of Leukocyte Biology

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“…Understanding the specific physiological reactions that cause these effects is an active area of research and another way mineralogy and geochemistry may provide valuable insight. For example, some mineral surfaces are known to generate free radicals at defects and electron hole-pair sites that may be an avenue of significant cellular destruction (Borda et al 2003;Cohn et al 2006;Dutta and Moudgil 2007).…”

Section: Introductionmentioning

confidence: 99%

Geochemistry in the lung: Reaction-path modeling and experimental examination of rock-forming minerals under physiologic conditions

Taunton

Gunter

Druschel

et al. 2010

American Mineralogist

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A novel and promising application of a geochemical tool adapted to medical science is the thermodynamic and kinetic modeling of the behavior of minerals in fluids similar to lung fluids (or simulated lung fluids, SLF). Reaction-path modeling for chrysotile, anorthite, K-feldspar, talc, muscovite, kaolinite, albite, and quartz under physiologic conditions in SLF gives dissolution times for these minerals as: chrysotile < anorthite < K-feldspar < talc < muscovite = kaolinite = albite = quartz. For the reaction of these minerals with SLF, hydroxylapatite (a mineral initially supersaturated in SLF) and several other secondary minerals were predicted to form (e.g., mesolite is predicted to precipitate during dissolution reactions of other Al 3+-containing minerals). Batch experiments using SLF and a brucite/chrysotile mineral mixture confirm that hydroxylapatite forms during reactions in SLF, potentially a function of having a seed crystal in the brucite, chrysotile, or hydromagnesite (predicted to form from brucite dissolution) present. Moreover, SEM analysis of lung tissue also confirms the formation of calcium phosphates (e.g., hydroxylapatite). Reaction-path modeling of minerals under physiologic conditions provides insight into mineral behavior in the body; predicted mineralization pathways associated with pleural plaques and the predicted formation of Al 3+-bearing minerals during reaction-path modeling deserve attention when considering pathologies in the body.

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“…This identified the crystalline material as silica based on the results of previous studies in which the chemical components of silica have been elucidated. 20 Albite, the material commonly identified within the selected lung and soil samples, is a ubiquitous silica salt and a common component of rock formation. One of the presumed origins of this feldspar in the topsoil, and possibly in the air of St. Kitts, is deposition from the transatlantic Saharan dust plume.…”

Section: Discussionmentioning

confidence: 99%

Histology, prevalence, and environmental sources for pulmonary silicates depositions in domestic and wild animals

et al. 2023

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The source and significance of pulmonary silicate crystals in animals and people are poorly understood. To estimate the prevalence and characterize the pulmonary crystalline material in animals from St. Kitts, tissue samples from dogs, horses, cattle, sheep, goats, pigs, chickens, mongooses, and monkeys were examined by light microscopy, scanning electron microscopy with energy-dispersive x-ray analysis (SEM/EDXA), and x-ray diffraction. Crystalline material was seen in 201 of 259 (77.6%) lung samples as perivascular and interstitial accumulations of heterogeneous crystalline particulate material, free or within macrophages (silicate-laden macrophages [SLMs]), mostly lacking evidence of chronic inflammation or fibrosis. The crystalline material was birefringent, basophilic on acid-fast, and composed of silicas on SEM/EDXA. Mongooses (100%) and monkeys (98%) had the highest prevalence of SLM, followed by cattle and chickens. Lesions were graded on a 3-point scale based on the histologic location and extent of silicates and SLM and were significantly more severe in mongooses (median = 3) than in monkeys (median = 2), dogs (median = 2), and chickens (median = 1). On EDXA, the crystalline material from lungs, air, and topsoil was composed of silicon, oxygen, aluminum, and iron, with a particulate matter size between 2.5 and 10 µm. We hypothesize Saharan dust, volcanic ash, topsoil, and rock quarry dust are potential sources of siliceous dust inhalation and SLM accumulations lacking chronic inflammation (silicosis); dust generation may be potentiated by road vehicle or wind suspension. Future investigations are warranted on the role of silicate inhalation and respiratory comorbidities in people, with monkeys, mongooses, or chickens serving as possible sentinels for exposure.

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Crystalline Silica Particles Mediated Lung Injury

Cited by 6 publications

References 41 publications

Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation

Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation

Geochemistry in the lung: Reaction-path modeling and experimental examination of rock-forming minerals under physiologic conditions

Histology, prevalence, and environmental sources for pulmonary silicates depositions in domestic and wild animals

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