Abstract
Silicosis is an untreatable occupational lung disease caused by chronic inhalation of crystalline silica. Cyclical release and reuptake of silica particles by macrophages and airway epithelial cells causes repeated tissue damage, characterized by widespread inflammation and progressive diffuse fibrosis. While inhalation is the main route of entry for silica particles in humans, most preclinical studies administer silica via the intratracheal route. In vivo mouse models of lung disease are valuable tools required to bridge the translational gap between in vitro cell culture and human disease. This chapter describes a mouse model of silicosis which mimics clinical features of human silicosis, as well as methods for intranasal instillation of silica and disease analysis. Lung tissue can be collected for histological assessment of silica particle distribution, inflammation, structural damage, and fibrosis in sections stained with hematoxylin and eosin or Masson’s trichrome. This approach can be extended to other chronic fibrotic lung diseases where inhalation of small damaging particles such as pollutants causes irreversible disease.
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References
Lam M, Mansell A, Tate MD (2022) Another one fights the dust: targeting the NLRP3 inflammasome for the treatment of silicosis. Am J Respir Cell Mol Biol 66:601–611
Hoy RF, Jeebhay MF, Cavalin C et al (2022) Current global perspectives on silicosis—convergence of old and newly emergent hazards. Respirology 27:387–398
Jones CM, Pasricha SS, Heinze SB, MacDonald S (2020) Silicosis in artificial stone workers: spectrum of radiological high-resolution CT chest findings. J Med Imaging Radiat Oncol 64:241–249
McDonald JW, Roggli VL (1995) Detection of silica particles in lung tissue by polarizing light microscopy. Arch Pathol Lab Med 119:242–246
Zhao Y, Hao C, Bao L et al (2020) Silica particles disorganize the polarization of pulmonary macrophages in mice. Ecotoxicol Environ Saf 193:110364
Yu Q, Fu G, Lin H et al (2020) Influence of silica particles on mucociliary structure and MUC5B expression in airways of C57BL/6 mice. Exp Lung Res 46:217–225
Adamcakova J, Mokra D (2021) New insights into pathomechanisms and treatment possibilities for lung silicosis. Int J Mol Sci 22:4162
Hornung V, Bauernfeind F, Halle A et al (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9:847–856
Biswas R, Hamilton RF, Holian A (2014) Role of lysosomes in silica-induced inflammasome activation and inflammation in absence of MARCO. J Immunol Res 2014:304180
Hamilton RF Jr, Thakur SA, Holian A (2008) Silica binding and toxicity in alveolar macrophages. Free Radic Biol Med 44:1246–1258
Jagirdar J, Begin R, Dufresne A et al (1996) Transforming growth factor-β (TGF-β) in silicosis. Am J Respir Crit Care Med 154:1076–1081
Doerner AM, Zuraw BL (2009) TGF-β1-induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids. Respir Res 10:100
Peeters PM, Perkins TN, Wouters EFM et al (2013) Silica induces NLRP3 inflammasome activation in human lung epithelial cells. Part Fibre Toxicol 10:3
Song M, Wang J, Sun Y et al (2022) Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages. Acta Pharmacol Sin 43:1274–1284
Chen S, Han B, Geng X et al (2022) Microcrystalline silica particles induce inflammatory response via pyroptosis in primary human respiratory epithelial cells. Environ Toxicol 37:385–400
Ong JDH, Mansell A, Tate MD (2017) Hero turned villain: NLRP3 inflammasome-induced inflammation during influenza A virus infection. J Leukoc Biol 101:863–874
Vince JE, Silke J (2016) The intersection of cell death and inflammasome activation. Cell Mol Life Sci 73:2349–2367
Song M, Wang J, Sun Y et al (2022) Inhibition of gasdermin D-dependent pyroptosis attenuates the progression of silica-induced pulmonary inflammation and fibrosis. Acta Pharm Sin B 12:1213–1224
Mayeux JM, Kono DH, Pollard KM (2019) Development of experimental silicosis in inbred and outbred mice depends on instillation volume. Sci Rep 9:1–10
Gulumian M, Borm PJA, Vallyathan V et al (2006) Mechanistically identified suitable biomarkers of exposure, effect, and susceptibility for silicosis and coal-worker’s pneumoconiosis: a comprehensive review. J Toxicol Environ Health 9:357–395
Cassel SL, Eisenbarth SC, Iyer SS et al (2008) The Nalp3 inflammasome is essential for the development of silicosis. Proc Natl Acad Sci USA 105:9035–9040
di Giuseppe M, Gambelli F, Hoyle GW et al (2009) Systemic inhibition of NF-ÎşB activation protects from silicosis. PLoS One 4:e5689
Sun J, Li Q, Lian X et al (2019) MicroRNA-29b mediates lung mesenchymal-epithelial transition and prevents lung fibrosis in the silicosis model. Mol Ther Nucleic Acids 14:20–31
Beamer CA, Migliaccio CT, Jessop F et al (2010) Innate immune processes are sufficient for driving silicosis in mice. J Leukoc Biol 88:547–557
Ortiz LA, Lasky J, Gozal E et al (2001) Tumor necrosis factor receptor deficiency alters matrix metalloproteinase 13/tissue inhibitor of metalloproteinase 1 expression in murine silicosis. Am J Respir Crit Care Med 163:244–252
Mansell A, Tate MD (2018) In vivo infection model of severe influenza A virus. Methods Mol Biol 1725:91–99
Borges VM, Lopes MF, Falcão H et al (2002) Apoptosis underlies immunopathogenic mechanisms in acute silicosis. Am J Respir Cell Mol Biol 27:78–84
Davis GS, Leslie KO, Hemenway DR (1998) Silicosis in mice: effects of dose, time, and genetic strain. J Environ Pathol Toxicol Oncol 17:81–97
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Lam, M., Mansell, A., Tate, M.D. (2023). Preclinical Mouse Model of Silicosis. In: Jenkins, B.J. (eds) Inflammation and Cancer. Methods in Molecular Biology, vol 2691. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3331-1_9
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DOI: https://doi.org/10.1007/978-1-0716-3331-1_9
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