Silicosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
- Silica (silicon dioxide) is the most abundant mineral on earth. Silica exists in crystalline and amorphous forms. Crystalline silica (quartz, cristobalite, and tridymite) is associated with a spectrum of pulmonary diseases. Amorphous forms, including vitreous silica and diatomite (formed from skeletons of prehistoric marine organisms), are relatively less toxic after inhalation [1].
- Quartz is the most abundant form of crystalline silica and is a major component of rocks including granite, slate, and sandstone. Granite contains about 30 percent free silica, slate about 40 percent, and sandstone is almost pure silica[2]. Cristobalite and tridymite occur naturally in lava and are formed when quartz or amorphous silica is subjected to very high temperatures.
- The toxicity of crystalline silica appears to result from the ability of crystalline silica surfaces to interact with aqueous media, to generate oxygen radicals, and to injure target pulmonary cells such as alveolar macrophages. Resultant generation of inflammatory cytokines (eg, interleukin-1 and tumor necrosis factor beta) by target cells lead to cytokine networking between inflammatory cells and resident pulmonary cells, resulting in inflammation and fibrosis [3].
- Lower intensity exposures to silica [4] evoke reversible inflammatory changes characterized by focal aggregations of mineral-laden alveolar macrophages, where as, higher exposures elicit intense and protracted inflammatory changes, cell proliferation in various compartments of the lung, and excessive deposition of collagen and other extracellular matrix components by mesenchymal cells. The AM is implicated as a major cell type in fibrogenesis [5]. In addition, various cell types of the immune system, including neutrophils[6], T-lymphocytes, and mast cells are also implicated in the development of fibrosis. A multiplicity of interactions between these effector cells and “target” cell types of injury, including bronchiolar, alveolar epithelial cells and fibroblasts, may govern the pathogenesis and progression of disease.
- Injury to the alveolar type I epithelial cell is regarded as an early event in fibrogenesis followed by hyperplasia and hypertrophy[7]of type II epithelial cells. Silica-induced cell hyperproliferation of mesenchymal cells is also a hallmark of the fibrotic lesion. Proliferation may occur intially at sites of accumulation of inhaled minerals, but later at distal sites where particles or fibers are translocated over time. Alternatively, mitogenic cytokines may mediate signaling events, leading to cell replication at sites physically remote from fibers (89, 90). The initiation of proliferation in epithelial cells and fibroblasts by silica may occur after upregulation of the early response protooncogenes, c-fos, c-jun, and c-myc [8].
- Increased expression of early response genes and protein products is also linked to the development of apoptosis [9][10]
References
- ↑ Merget R, Bauer T, Küpper HU, Philippou S, Bauer HD, Breitstadt R; et al. (2002). "Health hazards due to the inhalation of amorphous silica". Arch Toxicol. 75 (11–12): 625–34. PMID 11876495.
- ↑ Lapp NL (1981). "Lung disease secondary to inhalation of nonfibrous minerals". Clin Chest Med. 2 (2): 219–33. PMID 6273058.
- ↑ Rimal B, Greenberg AK, Rom WN (2005). "Basic pathogenetic mechanisms in silicosis: current understanding". Curr Opin Pulm Med. 11 (2): 169–73. PMID 15699791.
- ↑ Velan GM, Kumar RK, Cohen DD (1993). "Pulmonary inflammation and fibrosis following subacute inhalational exposure to silica: determinants of progression". Pathology. 25 (3): 282–90. PMID 8265248.
- ↑ Oberdörster G (1994). "Macrophage-associated responses to chrysotile". Ann Occup Hyg. 38 (4): 601–15, 421–2. PMID 7978983.
- ↑ Quinlan TR, BéruBé KA, Marsh JP, Janssen YM, Taishi P, Leslie KO; et al. (1995). "Patterns of inflammation, cell proliferation, and related gene expression in lung after inhalation of chrysotile asbestos". Am J Pathol. 147 (3): 728–39. PMC 1870980. PMID 7677184.
- ↑ Lesur O, Bouhadiba T, Melloni B, Cantin A, Whitsett JA, Bégin R (1995). "Alterations of surfactant lipid turnover in silicosis: evidence of a role for surfactant-associated protein A (SP-A)". Int J Exp Pathol. 76 (4): 287–98. PMC 1997178. PMID 7547443.
- ↑ Janssen YM, Heintz NH, Marsh JP, Borm PJ, Mossman BT (1994). "Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers". Am J Respir Cell Mol Biol. 11 (5): 522–30. doi:10.1165/ajrcmb.11.5.7946382. PMID 7946382.
- ↑ BéruBé KA, Quinlan TR, Fung H, Magae J, Vacek P, Taatjes DJ; et al. (1996). "Apoptosis is observed in mesothelial cells after exposure to crocidolite asbestos". Am J Respir Cell Mol Biol. 15 (1): 141–7. doi:10.1165/ajrcmb.15.1.8679218. PMID 8679218.
- ↑ Mossman BT, Churg A (1998). "Mechanisms in the pathogenesis of asbestosis and silicosis". Am J Respir Crit Care Med. 157 (5 Pt 1): 1666–80. doi:10.1164/ajrccm.157.5.9707141. PMID 9603153.