Abstract
Silicosis is caused by the inhalation of crystalline silica (silicon dioxide, SiO2) in various forms. This review proposes that the cascade of inflammatory and fibrotic events involved in cell-mediated, and possibly humoral, immune responses also produces silicosis. The hypothesis rests on the central concept that interactions between silica and pulmonary macrophages are the pivotal events in the pathogenesis of silicosis. Resident and recruited pulmonary macrophages demonstrate intimate contact with silica from the moment of deposition, and throughout the time the particles remain in the lung. The silica probably exerts its effects on the macrophages that ingest it by altering their function while they are alive, rather than merely by disrupting them. The macrophage appears to be stimulated to secrete mediator substances, such as interleukin-1 (IL-1), which alter the function and behavior of other cells. Lymphocytes and macrophages appear in close proximity to one another in developing silicotic nodules, and increased proportions of lymphocytes are found in bronchoalveolar lavage specimens from animals and humans with silica dust exposure. Hypothetically, macrophages influence and activate lymphocytes, which then feed back to amplify the response by stimulating the same or other recruited macrophages. An expanded and activated population of lymphocytes under the influence of IL-1 in turn can secrete a variety of lymphokines which profoundly alter monocyte/macrophage function. The macrophage has been implicated as a major cause for the fibrosis that accompanies silicosis. The products of activated T-lymphocytes, particularly interferon-gamma (IF-g), are potent stimulators of secretion from macrophages of a fibroblast growth competence factor, macrophage-derived growth factor (MDGF). IL-1 may have an additional stimulatory effect on fibroblasts. Neutrophils and macrophages also may be important in silicosis because of their potent ability to cause lung tissue injury. Silicosis provides a model of chronic diffuse interstitial immunologic and fibrotic lung disease in which the cause is known, can be applied in defined doses, and tracked in the lung throughout the course of the disease. Further studies should provide better understanding of the mechanisms that goven pulmonary injury, inflammation, repair, and fibrosis.
Similar content being viewed by others
References
Allison AC, Harington JS, Birbeck M (1966) An examination of the cytotoxic effects of silica on macrophages. J Exp Med 124:141–154
Bateman ED, Emerson RJ, Cole PJ (1982) A study of macrophage-mediated initiation of fibrosis by asbestos and silica using a diffusion chamber technique. Br J Exp Pathol 63:414–425
Brody AR, Hill LH, Adkins B, O’Connor RW (1981) Chrysotile asbestos inhalation in rats: deposition pattern and reaction of alveolar epithelium and pulmonary macrophages. Am Rev Respir Dis 123:670–679
Brody AR, Roe MW, Evans JN, Davis GS (1980) Use of backscattered electron imaging to quantify the distribution of inhaled crystalline silica. SEM 3:301–306
Brody AR, Roe MW, Evans JN, Davis GS (1982) Deposition and translocation of inhaled silica in rats. Quantification of particle distribution, macrophage participation, and function. Lab Invest 47:533–541
Buechner HA, Ansari A (1969) Acute silcoproteinosis: a new pathologic variant silicosis in sandblasters, characterized by histologic features resembling alveolar proteinosis. Dis Chest 55:274
Burrell R, Anderson M (1973) The induction of fibrogenesis by silica-treated alveolar macrophages. Environ Res 6:389–394
Calhoun WJ, Christman JW, Ershler WB, Graham GB, Davis GS (1985) Elevated immunoglobulins in the lavage fluid of healthy granite workers, Thorax, in press
Callis AH, Sohnle PG, Mandel GS, Wiessner J, Mandel NS (1985) Kinetics of inflammatory and fibrotic pulmonary changes in a murine model of silicosis. J Lab Clin Med 105:547–553
Christman JW, Emerson RJ, Graham GB, Davis GS (1985) Mineral dust and cell recovery from the bronchoalveolar lavage of healthy Vermont granite workers. Am Rev Respir Dis 132:393–399
Craighead JE, Vallyathan NV (1980) Cryptic pulmonary lesions in workers occupationally exposed to dust containing silica. JAMA 244:1939–1941
Dauber JH, Daniele RP (1980) Secretion of chemotaxins by guinea pig lung macrophages I: The spectrum of inflammatory cell responses. Exp Lung Res 1:23
Dauber JH, Rossman MD, Pietra GG, Jimenez SA, Daniele RP (1980) Experimental silicosis. Morphologic and biochemical abnormalities produced by intratracheal instillation of quartz into guinea pig lungs. Am J Pathol 101:595–607
Davis GS, Hemenway DR, Evans JN, Lapenas DJ, Brody AR (1981) Alveolar macrophage stimulation and population changes in silica-exposed rats. Chest 80S:8S-10S
deShazo RD (1982) Current concepts about the pathogenesis of silicosis and asbestosis. J Allergy Clin Immunol 70:41–49
Doll NJ, Stankus RP, Hughes J, Weill H, Gupta RC, Rodriguez M, Jones RN, Alspaugh MA, deSalvaggio JE (1981) Immune complexes and autoantibodies in silicosis. J Allergy Clin Immunol 68:281–285
Emerson RJ, Davis GS (1983) Effect of alveolar lining material-coated silica on rat alveolar macrophages. Environ Health Perspect 51:81–84
Gardner LU (1933) Pathology of so-called acute silicosis. Am J Public Health 23:1240
Green GM, Jakab GJ, Low RB, Davis GS (1977) State of the art: defense mechanisms of the respiratory membrane. Am Rev Respir Dis 115:479–514
Gross P, deTreville RTP (1968) Alveolar proteinosis: its experimental production in rodents. Arch Pathol 86:255–261
Harrington JS, Ritchie M, King PC, Miller K (1973) The in-vitro effects of silica-treated hamster macrophages on collagen production by hamster fibroblasts. J Pathol 109:21–37
Heppleston AG, Stiles JA (1967) Activity of a macrophage factor in collagen formation by silica. Nature (London) 214:521–522
Hounam RF, Morgan A (1977) Particle deposition. In: Brain JD, Proctor DF, Reid LM (eds): Respiratory defense mechanisms. Marcel Dekker, New York, pp 125–156
Kampschmidt RF (1984) The numerous postulated biological manifestations of interleukin-1. J Leukocyte Biol 36:341–355
Kelley J, Trombley L, Kovacs EJ, Davis GS, Absher M (1981) Pulmonary macrophages alter the collagen phenotype of lung fibroblasts. J Cell Physiol 109:353–361
Koskinen HA, Tiilikainen A, Nordman H (1983) Increased prevalence of HLA-Aw19 and of the phenogroup Aw19, B18 in advanced silicosis. Chest 83:848–852
Kovacs EJ, Kelley J (1985) Secretion of macrophage-derived growth factor during acute lung injury induced by bleomycin. J Leukocyte Biol 37:1–14
Kovacs EJ, Kelley J (1985) Lymphokine regulation of macrophage-derived growth factor secretion following pulmonary injury. Am J Pathol 121:261–268
Lowrie DB (1982) What goes wrong with the macrophage in silicosis: Eur J Respir Dis 63:180–182
Lugano EM, Dauber JH, Daniele RP (1981) Silica stimulation of chemotactic factor release by guinea pig alveolar macrophages. J Reticuloendothel Soc 30(5):381–390
Lugano EM, Dauber JH, Elias JA, Bashey RI, Jimenez SA, Daniele RP (1984) The regulation of lung fibroblast proliferation by alveolar macrophages in experimental silicosis. Am Rev Respir Dis 129:767–771
Martin TR, Altman LC, Albert RK, Henderson UR (1984) Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung. Am Rev Respir Dis 129:106
Merrill WW, Naegel GP, Matthay RA, Reynolds HY (1980) Alveolar macrophage-derived chemotactic factor—kinetics of in-vitro production and partial characterization. J Clin Invest 65:268–276
Nathan CF, Murray HW, Cohn ZA (1980) The macrophage as an effector cell. N Engl J Med 303:622–626
Reiser KM, Haschek WM, Hesterberg TW, Last JA (1983) Long-term effects of intratracheally instilled quartz on collagen metabolism and morphologic characteristics of rat lungs. Am J Pathol 110:30–40
Reynolds HY (1983) Lung inflammation: role of endogenous chemotactic factors in attracting polymorphonuclear granulocytes. Am Rev Respir Dis 127:S16-S25
Richards RJ, Wusteman FS (1974) The effects of silica dust and alveolar macrophages on lung fibroblasts grown in-vitro. Life Sci 14:355–364
Ruoslahti EE, Engvall E, Hayman EG (1981) Fibronectin: current concepts of its structure and functions. Collagen Res 1:95–128
Schmidt JA, Oliver CN, Lepe-Zuniga JL, Green I, Grey I (1984) Silica-stimulated monocytes release fibroblast proliferation factors identical to interleukin-1. A potential role for interleukin-1 in the pathogenesis of silicosis. J Clin Invest 73:1462–1472
Schuyler M, Zisking M, deSalvaggio J (1977) Cell-mediated immunity silicosis. Am Rev Respir Dis 116:147–151
Schuyler M, Gauner HR, Stankus RP, Kaimal V, Hoffman E, deSalvaggio J (1980) Bronchoalveolar lavage in silicosis. Lung 157:95–102
Snyder GL (1983) Interstitial pulmonary fibrosis—which cell is the culprit? Am Rev Respir Dis 128:535
Snyderman R, Shun HS, Dannenberg AM (1972) Macrophage proteinase and inflammation: The production of chemotactic activity from the fifth component of complement by macrophage proteinase. J Immunol 109:896
Spencer H (1977) Pathology of the lung. WB Saunders, Philadelphia, pp 379–395
Suratt PM, Winn WC, Brody AR, Bolton WK, Giles RD (1977) Acute silicosis in tombstone sandblasters. Am Rev Respir Dis 115:521–529
Unanue ER (1980) Cooperation between mononuclear phagocytes and lymphocytes in immunity. N Engl J Med 303:977–985
Wagner JC, Burns J, DeMunday, McGee J (1982) Presence of fibronectin in pneumoconiotic lesions. Thorax 37:54–56
Wharton W, Gillespie GY, Russell SW, Pledger (1982) Mitogenic activity elaborated by macrophage-like cell lines acts as a competence factor(s) for BALB/c 3T3 cells. J Cell Physiol 110:93–100
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Davis, G.S. Pathogenesis of silicosis: Current concepts and hypotheses. Lung 164, 139–154 (1986). https://doi.org/10.1007/BF02713638
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02713638