Silicosis pathophysiology: Difference between revisions
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*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. | *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. | ||
* Generation of inflammatory [[cytokines]] (eg, interleukin-1 and tumor necrosis factor beta) by target cells results in cytokine networking between inflammatory cells and resident pulmonary cells, which in turn leads to inflammation and fibrosis.<ref name="pmid15699791">{{cite journal| author=Rimal B, Greenberg AK, Rom WN| title=Basic pathogenetic mechanisms in silicosis: current understanding. | journal=Curr Opin Pulm Med | year= 2005 | volume= 11 | issue= 2 | pages= 169-73 | pmid=15699791 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15699791 }} </ref> | * Generation of inflammatory [[cytokines]] (eg, interleukin-1 and tumor necrosis factor beta) by target cells results in cytokine networking between inflammatory cells and resident pulmonary cells, which in turn leads to inflammation and fibrosis.<ref name="pmid15699791">{{cite journal| author=Rimal B, Greenberg AK, Rom WN| title=Basic pathogenetic mechanisms in silicosis: current understanding. | journal=Curr Opin Pulm Med | year= 2005 | volume= 11 | issue= 2 | pages= 169-73 | pmid=15699791 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15699791 }} </ref> | ||
* The alveolar macrophages are implicated as the major cell type in fibrogenesis<ref name=" | * The alveolar macrophages are implicated as the major cell type in fibrogenesis<ref name="pmid7978983">{{cite journal| author=Oberdörster G| title=Macrophage-associated responses to chrysotile. | journal=Ann Occup Hyg | year= 1994 | volume= 38 | issue= 4 | pages= 601-15, 421-2 | pmid=7978983 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7978983 ; }} </ref>, but other immune cells, namely neutrophils<ref name="pmid7677184">{{cite journal| author=Quinlan TR, BéruBé KA, Marsh JP, Janssen YM, Taishi P, Leslie KO et al.| title=Patterns of inflammation, cell proliferation, and related gene expression in lung after inhalation of chrysotile asbestos. | journal=Am J Pathol | year= 1995 | volume= 147 | issue= 3 | pages= 728-39 | pmid=7677184 | doi= | pmc=PMC1870980 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7677184 ; }} </ref>, T-lymphocytes, and mast cells are also involved. | ||
* Following the interaction between effector immune cells (such as alveolar macrophage) and target tissue (such as bronchiolar/alveolar epithelial cells, [[fibroblasts]]), the progression of the disease is poorly understand. | * Following the interaction between effector immune cells (such as alveolar macrophage) and target tissue (such as bronchiolar/alveolar epithelial cells, [[fibroblasts]]), the progression of the disease is poorly understand. | ||
** Injury to the alveolar type I epithelial cell is regarded as an early event in [[fibrogenesis]] followed by [[hyperplasia]] and [[hypertrophy]]<ref name="pmid75474432"></ref>of type II epithelial cells. | ** Injury to the alveolar type I epithelial cell is regarded as an early event in [[fibrogenesis]] followed by [[hyperplasia]] and [[hypertrophy]]<ref name="pmid75474432"></ref>of type II epithelial cells. | ||
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** Alternatively, mitogenic cytokines may mediate signaling events, leading to cell replication at sites physically remote from fibers. | ** Alternatively, mitogenic cytokines may mediate signaling events, leading to cell replication at sites physically remote from fibers. | ||
** The initiation of proliferation in epithelial cells and [[fibroblasts]] by [[silica]] may occur following the upregulation of the early response proto-oncogenes C-FOS, C-JUN, and C-MYC.<ref name="pmid79463822"></ref> | ** The initiation of proliferation in epithelial cells and [[fibroblasts]] by [[silica]] may occur following the upregulation of the early response proto-oncogenes C-FOS, C-JUN, and C-MYC.<ref name="pmid79463822"></ref> | ||
** Increased expression of early response genes and protein products is also linked to the development of [[apoptosis]]<ref name=" | ** Increased expression of early response genes and protein products is also linked to the development of [[apoptosis]]<ref name="pmid8679218">{{cite journal| author=BéruBé KA, Quinlan TR, Fung H, Magae J, Vacek P, Taatjes DJ et al.| title=Apoptosis is observed in mesothelial cells after exposure to crocidolite asbestos. | journal=Am J Respir Cell Mol Biol | year= 1996 | volume= 15 | issue= 1 | pages= 141-7 | pmid=8679218 | doi=10.1165/ajrcmb.15.1.8679218 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8679218 ; }} </ref><ref name="pmid9603153">{{cite journal| author=Mossman BT, Churg A| title=Mechanisms in the pathogenesis of asbestosis and silicosis. | journal=Am J Respir Crit Care Med | year= 1998 | volume= 157 | issue= 5 Pt 1 | pages= 1666-80 | pmid=9603153 | doi=10.1164/ajrccm.157.5.9707141 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9603153 }} </ref> | ||
=== Low Intensity Exposure vs. High Intensity Exposure === | === Low Intensity Exposure vs. High Intensity Exposure === | ||
* Lower intensity exposures to silica evoke reversible inflammatory changes characterized by focal aggregations of mineral-laden alveolar [[Macrophages|macrophages.]]<ref name="pmid8265248">{{cite journal| author=Velan GM, Kumar RK, Cohen DD| title=Pulmonary inflammation and fibrosis following subacute inhalational exposure to silica: determinants of progression. | journal=Pathology | year= 1993 | volume= 25 | issue= 3 | pages= 282-90 | pmid=8265248 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8265248 }} </ref> | * Lower intensity exposures to silica evoke reversible inflammatory changes characterized by focal aggregations of mineral-laden alveolar [[Macrophages|macrophages.]]<ref name="pmid8265248">{{cite journal| author=Velan GM, Kumar RK, Cohen DD| title=Pulmonary inflammation and fibrosis following subacute inhalational exposure to silica: determinants of progression. | journal=Pathology | year= 1993 | volume= 25 | issue= 3 | pages= 282-90 | pmid=8265248 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8265248 }} </ref> | ||
* In contrast, 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. | * In contrast, 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. | ||
==References== | ==References== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]
Overview
The toxicity of crystalline silica results 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. Generation of inflammatory cytokines (eg, interleukin-1 and tumor necrosis factor beta) by target cells results in cytokine networking between inflammatory cells and resident pulmonary cells, which in turn leads to inflammation and fibrosis.
Pathophysiology
Pathogenesis
- 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.
- Generation of inflammatory cytokines (eg, interleukin-1 and tumor necrosis factor beta) by target cells results in cytokine networking between inflammatory cells and resident pulmonary cells, which in turn leads to inflammation and fibrosis.[1]
- The alveolar macrophages are implicated as the major cell type in fibrogenesis[2], but other immune cells, namely neutrophils[3], T-lymphocytes, and mast cells are also involved.
- Following the interaction between effector immune cells (such as alveolar macrophage) and target tissue (such as bronchiolar/alveolar epithelial cells, fibroblasts), the progression of the disease is poorly understand.
- Injury to the alveolar type I epithelial cell is regarded as an early event in fibrogenesis followed by hyperplasia and hypertrophy[4]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.
- The initiation of proliferation in epithelial cells and fibroblasts by silica may occur following the upregulation of the early response proto-oncogenes C-FOS, C-JUN, and C-MYC.[5]
- Increased expression of early response genes and protein products is also linked to the development of apoptosis[6][7]
Low Intensity Exposure vs. High Intensity Exposure
- Lower intensity exposures to silica evoke reversible inflammatory changes characterized by focal aggregations of mineral-laden alveolar macrophages.[8]
- In contrast, 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.
References
- ↑ Rimal B, Greenberg AK, Rom WN (2005). "Basic pathogenetic mechanisms in silicosis: current understanding". Curr Opin Pulm Med. 11 (2): 169–73. PMID 15699791.
- ↑ Oberdörster G (1994). ; "Macrophage-associated responses to chrysotile" Check
|url=value (help). 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" Check
|url=value (help). Am J Pathol. 147 (3): 728–39. PMC 1870980. PMID 7677184. - ↑
- ↑
- ↑ 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" Check
|url=value (help). 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.
- ↑ 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.