Abstract
Numerous investigations have been conducted to elucidate mechanisms involved in the initiation and progression of silicosis. However, most of these studies involved bolus exposure of rats to silica, i.e. intratracheal instillation or a short duration inhalation exposure to a high dose of silica. Therefore, the question of pulmonary overload has been an issue in these studies. The objective of the current investigation was to monitor the time course of pulmonary reactions of rats exposed by inhalation to a non-overload level of crystalline silica. To accomplish this, rats were exposed to 15 mg/m3silica, 6 h/day, 5 days/week for up to 116 days of exposure. At various times (5-116 days exposure), animals were sacrificed and silica lung burden, lung damage, inflammation, NF-KB activation, reactive oxygen species and nitric oxide production, cytokine production, alveolar type II epithelial cell activity, and fibrosis were monitored. Activation of NF-KB/DNA binding in BAL cells was evident after 5 days of silica inhalation and increased linearly with continued exposure. Parameters of pulmonary damage, inflammation and alveolar type II epithelial cell activity rapidly increased to a significantly elevated but stable new level through the first 41 days of exposure and increased at a steep rate thereafter. Pulmonary fibrosis was measurable only after this explosive rise in lung damage and inflammation, as was the steep increase in TNF-a and IL-1 production from BAL cells and the dramatic rise in lavageable alveolar macrophages. Indicators of oxidant stress and pulmonary production of nitric oxide exhibited a time course which was similar to that for lung damage and inflammation with the steep rise correlating with initiation of pulmonary fibrosis. Staining for iNOS and nitrotyrosine was localized in granulomatous regions of the lung and bronchial associated lymphoid tissue. Therefore, these data demonstrate that the generation of oxidants and nitric oxide, in particular, is temporally and anatomically associated with the development of lung damage, inflammation, granulomas and fibrosis. This suggests an important role for nitric oxide in the initiation of silicosis. (Mol Cell Biochem 234/235: 177–184, 2002)
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Driscoll KE, Guthrie GD: Crystalline silica and silicosis. In: R.A. Roth (ed), Comprehensive Toxicology. Vol 8. Toxicology of the Respiratory System. Elsevier Science, New York, 1997, pp 373–392
Lapp NL, Castranova V: How silicosis and coal workers’ pneumoconiosis develop — a cellular assessment. Occup Med State Art Rev 8: 35–56,1993
Castranova V, Vallyathan V: Silicosis and coal workers’ pneumoconiosis. Environ Health Perspect 108 (suppl 4): 675–684, 2000
Castranova V: From coal mine dust to quartz: Mechanisms of pulmonary pathogenicity. Inhal Toxicol 12 (suppl 3): 7–14, 2000
ILSI Risk Science Institute Workshop Participants: The relevance of the rat lung response to particle overload for human risk assessment: A workshop consensus report. Inhal Toxicol 12: 1–17, 2000
Porter DW, Ramsey D, Hubbs AF, Battelli L, Ma J, Barger M, Landsittel D, Robinson VA, McLaurin J, Khan A, Jones W, Teass A, Castranova V: Time course of pulmonary response of rats to inhalation of crystalline silica: Histological results and biochemical indices of damage, lipidosis and fibrosis. J Environ Pathol Toxicol Oncol 20: 1–14, 2001
Castranova V, Bowman L, Miles P: Transmembrane potential and ionic content of rat alveolar macrophages. J Cell Physiol 101: 471–479, 1979
Oyarzun MJ, Clements JA: Control of lung surfactant by ventilation, adrenergic mediators, and prostaglandins in the rabbit. Am Rev Respir Dis 117: 879–891,1978
Vallyathan V, Leonard S, Kuppusamy P, Pack D, Chzhan M, Sanders SP, Zweir JL: Oxidative stress in silicosis: Evidence for the enhanced clearance of free radicals from whole lungs. MolCellBiochem 168: 125–132,1997
Porter DW, Millecchia L, Robinson VA, Hubbs A, Willard P, Pack D, Ramsey D, McLaurin J, Khan A, Landsittel D, Teass A, Castranova V: Enhanced nitric oxide and reactive oxygen species production and damage after inhalation of silica. Am J Physiol Lung Cell Mol Physiol 2002 (in press)
Porter DW, Ye J, Ma J, Barger M, Robinson VA, Ramsey D, McLaurin J, Khan A, Landsittel D, Teass A, Castranova V: Time course of pulmonary response of rats to inhalation of crystalline silica: NF-03 activation, inflammation, cytokine production and damage. Inhal Toxicol 14: 101–119, 2002
lsshiki H, Akira S, Tanabe O, Nakajlmat, Shimamoto T, Hirano T, Kishimoto T: Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1 responsive element in the IL-6 gene. Mol Cell Biol 10: 2757–2764,1990
Kang JH, Lewis DM, Castranova V, Rojanasakul Y, Banks DE, Ma JY, Ma JK: Inhibitory action of tetrandrine on macrophage production of interleukin-1 (IL-1)-like activity and thymocyte proliferation. Exp Lung Res 18: 715–729, 1992
Kivirikko KI, Laitinen O, Prockop DJ: Modifications of a specific assay for hydroxyproline in urine. Annu Biol Chem 19: 249–255, 1967
Oberdorster G, Ferin J, Morrow PE: Volumetric loading of alveolar macrophages (AM): A possible basis for AM-mediated particle clearance. Exp Lung Res 18: 87–104, 1992
Miller FJ: Dosimetry of particles in laboratory animals and humans in relationship to issues surrounding lung overload and human health risk assessment: A critical review. Inhal Toxicol 12: 19–57, 2000
Chen F, Castranova V, Shi X, Demers LM: New insights into the role of nuclear factor-KB, an ubiquitous transcription factor in the initiation of diseases. Clin Chem 45: 7–17, 1999
Chen F, Yongju Y, Demers LM, Rojanasakul Y, Shi X, Vallyathan V, Castranova V: Role of hydroxyl radical in silica-induced NF-KB activation in macrophages. Annals Clin Lab Sci 28: 1–13, 1998
Kang JL, Go YH, Hur KC, Castranova V: Silica-induced nuclear factor-KB activation: Involvement of reactive oxygen species and protein tyrosine kinase activation. J Toxicol Environ Health 60: 27–46, 2000
Sacks M, Gordon J, Bylander J, Porter D, Shi X, Castranova V, Reasor MJ, Kaczmarczyk W, VanDyke K: Silica-induced pulmonary inflammation in rats: Activation of NF-KB and its suppression by dexamethasone. Biochem Biophys Res Commun 253: 181–184, 1998
Collart M, Bueuerle P, Vassalli P: Regulation of tumor necrosis fac tor alpha transcription in macrophages: Involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. Mol Cell Biol 10: 1498–1506, 1990
Barnes PL, Karin M: A pivotal transcription factor in chronic inflammatory diseases. New Engl J Med 366: 1066–1071, 1997
Driscoll KE, Lindenschmidt RC, Maurer JK, Higgins JM, Ridder G: Pulmonary response to silica or titanium dioxide: Inflammatory cells, alveolar macrophage-derived cytokines, and histology. Am J Respir Cell Mol Biol 2: 381–390, 1990
Piguet PF, Collart MA, Grau GE, Sappino AP, Vassalli P: Requirement for tumor necrosis factor for development of silica-induced pulmonary fibrosis. Nature 344: 245–247, 1990
Driscoll KE: The role of interleukin-1 and tumor necrosis factor-a in the lung’s response to silica. In: V. Castranova, V. Vallyathan, W.E. Wallace (eds), Silica and Silica-Induced Lung Diseases. CRC Press, Boca Raton, 1996, pp. 163–184
Vallyathan V, Goins M, Lapp L, Pack D, Leonard S, Shi X, Castranova V: Changes in bronchoalveolar lavage indices associated with radiographic classification in coal miners. Am J Respir Crit Care Med 162: 958–965,2000
Kuempel ED, Tran C-L, Bailer AL Porter DW, Hubbs AF, Castranova V: Biological and statistical approaches to predicting human lung cancer risk from silica. J Environ Path Toxicol Oncol 20 (suppl 1): 1532, 2001
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media New York
About this chapter
Cite this chapter
Castranova, V., Porter, D., Millecchia, L., Ma, J.Y.C., Hubbs, A.F., Teass, A. (2002). Effect of inhaled crystalline silica in a rat model: Time course of pulmonary reactions. In: Vallyathan, V., Shi, X., Castranova, V. (eds) Oxygen/Nitrogen Radicals: Cell Injury and Disease. Developments in Molecular and Cellular Biochemistry, vol 37. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1087-1_20
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1087-1_20
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5388-1
Online ISBN: 978-1-4615-1087-1
eBook Packages: Springer Book Archive