Silica binding and toxicity in alveolar macrophages
Open accessAbstract
Inhalation of the crystalline form of silica is associated with a variety of pathologies, from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science investigators looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage interacts with the inhaled silica particle and the consequences of silica-induced toxicity on the cellular level. Based on experimental results, several rationales have been developed for exactly how crystalline silica particles are toxic to the macrophage cell that is functionally responsible for clearance of the foreign particle. For example, silica is capable of producing reactive oxygen species (ROS) either directly (on the particle surface) or indirectly (produced by the cell as a response to silica), triggering cell-signaling pathways initiating cytokine release and apoptosis. With murine macrophages, reactive nitrogen species are produced in the initial respiratory burst in addition to ROS. An alternative explanation for silica toxicity includes lysosomal permeability, by which silica disrupts the normal internalization process leading to cytokine release and cell death. Still other research has focused on the cell surface receptors (collectively known as scavenger receptors) involved in silica binding and internalization. The silica-induced cytokine release and apoptosis are described as the function of receptor-mediated signaling rather than free radical damage. Current research ideas on silica toxicity and binding in the alveolar macrophage are reviewed and discussed.
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From An investigation of the internal morphology of asbestos ferruginous bodies: constraining their role in the onset of malignant mesothelioma (2023) · cites this paper as [18]
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Morris, A. S., Adamcakova‐Dodd, A., Lehman, S. E., Wongrakpanich, A., Thorne, P. S., Larsen, S. C., & Salem, A. K. (2015) · Toxicology Letters · doi:10.1016/j.toxlet.2015.11.006 · Cited by 54 · see citing works
Allemailem, K. S., Almatroudi, A., Alrumaihi, F., Almatroodi, S. A., Alkurbi, M. O., Basfar, G. T., Rahmani, A. H., & Khan, A. A. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s321343 · Cited by 52 · see citing works
Immunity to the Dual Threat of Silica Exposure and Mycobacterium tuberculosis
Konečný, P., Ehrlich, R. I., Gulumian, M., & Jacobs, M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2018.03069 · Cited by 51 · see citing works
Silica-Triggered Autoimmunity in Lupus-Prone Mice Blocked by Docosahexaenoic Acid Consumption
Bates, M. A., Brandenberger, C., Langohr, I. M., Kumagai, K., Lock, A. L., Harkema, J. R., Holian, A., & Pestka, J. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0160622 · Cited by 51 · see citing works
Self-citationClimate change, air quality, and respiratory health: a focus on particle deposition in the lungs
Chang, J.-H., Lee, Y.-L., Chang, L.-T., Chang, T.-Y., Hsiao, T.-C., Chung, K. F., Ho, K. F., Kuo, H.-P., Lee, K.-Y., Chuang, K.-J., et al. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2264881 · Cited by 49 · see citing works
Interferon β-Mediated Protective Functions of Microglia in Central Nervous System Autoimmunity
Scheu, S., Ali, S., Mann‐Nüttel, R., Richter, L., Arolt, V., Dannlowski, U., Kuhlmann, T., Klotz, L., & Alferink, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20010190 · Cited by 48 · see citing works
Uncoupling between Inflammatory and Fibrotic Responses to Silica: Evidence from MyD88 Knockout Mice
Re, S. L., Yakoub, Y., Devosse, R., Uwambayinema, F., Couillin, I., Ryffel, B., Marbaix, É., Lison, D., & Huaux, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099383 · Cited by 48 · see citing works
Aryl Hydrocarbon Receptor (AhR) Regulates Silica-Induced Inflammation But Not Fibrosis
Beamer, C. A., Seaver, B. P., & Shepherd, D. M. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs024 · Cited by 48 · see citing works
A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip
Sengupta, A., Dorn, A., Jamshidi, M., Schwob, M., Hassan, W. M., Maddalena, L. L. D., Hugi, A., Stucki, A., Dorn, P., Marti, T. M., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1114739 · Cited by 47 · see citing works
Imipramine blocks acute silicosis in a mouse model
Biswas, R., Trout, K. L., Jessop, F., Harkema, J. R., & Holian, A. (2017) · Particle and Fibre Toxicology · doi:10.1186/s12989-017-0217-1 · Cited by 47 · see citing works
Self-citationHe, X., Chen, S., Li, C. R., Ban, J., Wei, Y., He, Y., Liu, F., Chen, Y., & Chen, J. (2020) · Cells · doi:10.3390/cells9010122 · Cited by 47 · see citing works
Progressive massive fibrosis: An overview of the recent literature
Weissman, D. N. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108232 · Cited by 46 · see citing works
- Authors
- Hamilton, R. F., Thakur, S. A., & Holian, A.
- Affiliations
- University of Montana (US)
- Corresponding author
- Holian, Andrij
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 44
- Issue
- 7
- Pages
- 1246-1258
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC2680955
- OpenAlex
- W2044353844
- Cited by
- 415
- References
- 124
- Citations by year
- 2026: 19 · 2025: 16 · 2024: 25 · 2023: 33 · 2022: 32 · 2021: 33 · 2020: 23 · 2019: 21 · 2018: 24 · 2017: 22 · 2016: 23 · 2015: 16 · 2014: 19 · 2013: 23 · 2012: 18
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (P30GM103338)
- National Institute of Environmental Health Sciences (R01ES015294, ES-015294)
- National Center for Research Resources (P20RR017670)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Physiology › Sarcoidosis and Beryllium Toxicity Research
- Keywords
- crystalline silica, silica toxicity, alveolar macrophages, reactive oxygen species, reactive nitrogen species, respiratory burst, cytokine production, apoptosis, scavenger receptors, silicosis, particle clearance
- MeSH terms
- Animals, Free Radicals, Humans, Lung, Lysosomes, Macrophages, Models, Biological, Protein Binding, Silicon Dioxide, Surface-Active Agents, Signal Transduction, Macrophages, Alveolar, Apoptosis, Reactive Nitrogen Species, Mice
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