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Inflammatory response of the lung to tungsten particles: An experimental study in mice submitted to intratracheal instillation of a calcium tungstate powder

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Abstract

Tungsten has been implicated as a cause of a severe form of pneumoconiosis in humans, the so-called “hard metal” lung disease. We have investigated the effect of intratracheal instillation of a powder of calcium tungstate on the pulmonary tissue of CD-1 mice. The tungsten-induced alterations were studied using 3 microanatomical methods: cytologic study of exudates obtained by bronchoalveolar lavage (BAL); histologic examination of paraffin-embedded sections of the lung; and scanning electron microscopic (SEM) examination of lung samples using x-ray microanalysis to detect tungsten in situ. The animals were sacrificed 1, 3, 7, 14, and 21 days after a single intratracheal instillation of 250 µg calcium tungstate particles suspended in 100 µl of saline. We found that the metal particles induced a marked inflammatory response in the bronchoalveolar space characterized by a biphasic attraction of leukocytes with cellular peaks observed at day 1 and 14. More than 50% of the BAL macrophages showed ingested tungsten. In the lung parenchyma, the inflammatory infiltrates were predominantly located at the periphery of the bronchiolar walls. From 7 days on after the tungsten deposition, large inflammatory exudates were seen invading focal areas of the alveolar domain of the lung. SEM views revealed that the tungsten particles could be inside alveolar macrophages, in cells making up the alveolar wall, or inside periacinar lymphatics. Our data document that tungsten particles cause a marked inflammatory response in the lung tissue and that the leukocyte exudates may invade alveolar areas of the lung. This strong inflammatory response may correspond to the early stages of the tungsten-induced “hard-metal” lung disease previously reported in humans.

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References

  1. Adamson IYR, Bowden D (1980) Role of monocytes and interstitial cells in the generation of alveolar macrophages: kinetic studies after carbon loading. Lab Invest 42:518–523

    Google Scholar 

  2. Águas AP, Grande NR, Carvalho E (1991) Inflammatory macrophages in the dog contain high amounts of intravesicular ferritin and are associated with pouches of connective tissue fibers. Am J Anat 190:89–96

    Google Scholar 

  3. Alexandersson R (1988) Blood and urine concentrations as estimators of cobalt exposure. Arch Environ Health 43:299–303

    Google Scholar 

  4. Anderson BO, Bensard DD, Brown JM, Repine JE, Shanley PF, Leff JA, Terada AB, Harken AH (1991) FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms. Am J Physiol 260:R413-R420

    Google Scholar 

  5. Brieland JK, Kunkel RG, Fantone JC (1987) Pulmonary alveolar macrophage function during acute inflammatory lung injury. Am Rev Respir Dis 13:1300–1306

    Google Scholar 

  6. Brody AR, Hill LH, Adkins B, O'Connor RW (1981) Chrysotile asbestos inhalation in rats: deposition pattern and reaction of alveolar ephitelium and pulmonary macrophages. Am Rev Respir Dis 123:670–678

    Google Scholar 

  7. Corrin B (1970) Phagocytic potential of pulmonary alveolar epithelium with particular reference to surfactant metabolism. Thorax 25:110–115

    Google Scholar 

  8. Corrin B (1990) Occupational diseases of the lung. In: Symmers W St C, Corrin B (eds) The lungs, vol. 5. Churchill Livingstone, Edinburgh, pp 235–261

    Google Scholar 

  9. Crapo JD, Barry BE, Gehr P, Bachofen M, Weibel ER (1982) Number and cell characteristics of the normal human lung. Am Rev Respir Dis 125:740–745

    Google Scholar 

  10. Cugell DW, Morgan WKC, Perkins DG, Rubin A (1990) The respiratory effects of cobalt. Arch Intern Med 150:177–183

    Google Scholar 

  11. Cugell DW (1992) The hard metal diseases. Clin Chest Med 13:269–279

    Google Scholar 

  12. 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 101:595–612

    Google Scholar 

  13. Davis GS (1986) Pathogenesis of silicosis. Current concepts and hypothesis. Lung 164:139–154

    Google Scholar 

  14. Davis WB, Crystal KG (1984) Chronic interstitial lung disease. In: Simmons D (ed) Current pulmonology, vol. V. Wiley, New York, pp 347–473

    Google Scholar 

  15. Davison AG, Haslam PL, Corrin B (1983) Interstitial lung disease and asthma in hard-metal workers: bronchoalveolar lavage, ultrastructural, and analytical findings and results of bronchial provocation tests. Thorax 38:119–128

    Google Scholar 

  16. Doig AT (1976) Baritosis: a benign pneumoconiosis. Thorax 31:30–39

    Google Scholar 

  17. Grande NR, Sá CM, Águas AP, Carvalho E, Soares M (1990) Time course and distribution of tungsten-laden macrophages in the hilar lymph nodes of the dog lung after experimental instillation of calcium tungstate into the left apical bronchus. Lymphology 23:171–182

    Google Scholar 

  18. Grande NR, Pereira AS, Peão MND, Águas AP (1992) Embryological and structural basis of respiractory function. In: Freitas e Costa M (ed) Clinical pneumology, vol. 1. Lisbon Medical School Press, Lisbon, pp 15–39

    Google Scholar 

  19. Green FHY, Laquer WA (1980) Coal workers' pneumoconiosis. Pathol Annu 15:333–410

    Google Scholar 

  20. Lasfargues G, Lison D, Maldague P, Lauwerys R (1992) Comparative study of the acute lung toxicity of pure cobalt powder and cobalt-tungsten carbide mixture in rat. Toxicol Appl Pharmacol 112:41–50

    Google Scholar 

  21. Lehnert BE, Morrow PE (1985) Characteristics of alveolar macrophages following the deposition of a low burden of iron oxide in the lung. J Tox Environ Health 16:855–868

    Google Scholar 

  22. Morgan WKC, Seaton A (1984) Occupational lung disease, 2nd ed. WB Saunders, Philadelphia

    Google Scholar 

  23. Netter FH (1980) Reactions produced by metals and mixed dusts. In: Divertie MB (ed) Respiratory system, vol VII. Ciba Geigy Corp., Summit, NJ, pp 212–214

    Google Scholar 

  24. Ohori NP, Sciurba FC, Owens GR, et al (1989) Giant-cell interstitial pneumonia and hard-metal pneumoconiosis. Am J Surg Pathol 13:581–587

    Article  Google Scholar 

  25. Peão MND, Àguas AP, Sá MC, Grande NR (1992) Structural artifacts and advantages of cytocentrifugation of cells as viewed by scanning electron microscopy. Scanning microsc 6:281–285

    Google Scholar 

  26. Peão MND, Águas AP, de Sá CM, Pereira AS, Grande NR (1993) Scanning electron microscopy of the deep lymphatic network of the murine lung as viewed in corrosion casts. Lymphology 26:(in press)

  27. Peão MND, Àguas AP, Grande NR (1992) Cellular kinetics of inflammation in the pleural space of mice in response to the injection of exogenous particles. Exp Lung Res 18:863–876

    Google Scholar 

  28. Rizzato G, Lo CS, Barberis M, et al (1986) Trace of metal exposure in hard metal lung disease. Chest 90:101–106

    Google Scholar 

  29. Rom WN, Crystal RG (1991) Consequences of chronic inorganic dust exposure. In: Crystal RG, West JB (eds) The lung: scientific foundations, Vol. I. Raven Press, New York, pp 1885–1897

    Google Scholar 

  30. Rütttner JR, Spycher MA, Stolkin I (1987) Inorganic particulates in pneumoconiotic lungs of hard metal grinders. Br J Ind Med 44:657–660

    Google Scholar 

  31. Selikoff IJ, Lee DHK (1978) Asbestos and disease. Academic Press, New York

    Google Scholar 

  32. Silva MT, Appelberg R, Silva MNT, Macedo PM (1987) In vivo killing and degradation of Mycobacterium aurum within mouse peritoneal macrophages. Infect Immun 55:2006–2016

    Google Scholar 

  33. Sjogren I, Hillerdal G, Andersson A, et al (1980) Hard metal lung disease: importance of cobalt in coolants. Thorax 35:653–659

    Google Scholar 

  34. van Sprundel MPM (1990) Pneumoconiosis: the situation in developing countries. Exp Lung Res 16:5–13

    Google Scholar 

  35. Warheit DB, Hansen JF, Hartsky MA (1991) Physiological and pathophysiological pulmonary responses to inhaled nuisance-like or fibrogenic dusts. Anat Rec 231:107–118

    Google Scholar 

  36. Weibel ER, Gehr P, Haies D, Gil J, Bschofen M (1976) The cell population of the normal lung. In: Bouhuys A (ed) Lung cells in disease. North-Holland Publishing Co., Amsterdam, pp 3–16

    Google Scholar 

  37. Weiss L (1988) A Textbook of histology, 6th ed. Urban and Schwarzenberg, Baltimore

    Google Scholar 

  38. Williams WJ (1988) Beryllium disease. Postgrad Med J 64:511–516

    Article  CAS  PubMed  Google Scholar 

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Peão, M.N.D., Águas, A.P., de Sá, C.M. et al. Inflammatory response of the lung to tungsten particles: An experimental study in mice submitted to intratracheal instillation of a calcium tungstate powder. Lung 171, 187–201 (1993). https://doi.org/10.1007/BF00203719

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