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British Journal of Industrial Medicine logoLink to British Journal of Industrial Medicine
. 1989 Dec;46(12):866–872. doi: 10.1136/oem.46.12.866

Inflammatory responses in lungs of rats inhaling coalmine dust: enhanced proteolysis of fibronectin by bronchoalveolar leukocytes.

G M Brown 1, K Donaldson 1
PMCID: PMC1009884  PMID: 2692694

Abstract

Chronic exposure to coalmine dust is associated with the accumulation of inflammatory leukocytes in the bronchoalveolar region of the lung and, in the long term, with fibrosis and emphysema of the lung parenchyma. Degradation of connective tissue by inflammatory leukocytes has been implicated in the parenchymal damage that precedes the development of fibrotic or emphysematous lesions in the lung. The ability of inflammatory leukocytes obtained by bronchoalveolar lavage from rats inhaling coalmine dust to degrade fibronectin in vitro was assessed. The animals were exposed to an airborne mass concentration of dust similar to the maximum permissible level in United Kingdom collieries. The bronchoalveolar lavage cell population showed changes with duration of dust exposure; there were increases in the total number of leukocytes and in the percentage of polymorphonuclear leukocytes, and the macrophage component of the lavage became increasingly activated, as assessed by the ability of these cells to spread on glass. In addition, degradation of a radiolabelled fibronectin matrix by the coalmine dust exposed bronchoalveolar leukocytes increased with duration of dust exposure. Thus exposure to airborne coalmine dust causes an influx of inflammatory leukocytes to the alveolar region. These cells have enhanced ability to degrade fibronectin and this may be important in subsequent disease development.

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Selected References

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  1. Beckett S. T. The generation and evaluation of UICC asbestos clouds in animal exposure chambers. Ann Occup Hyg. 1975 Dec;18(3):187–198. doi: 10.1093/annhyg/18.3.187. [DOI] [PubMed] [Google Scholar]
  2. Bolton R. E., Addison J., Davis J. M., Donaldson K., Jones A. D., Miller B. G., Wright A. Effects of the inhalation of dusts from calcium silicate insulation materials in laboratory rats. Environ Res. 1986 Feb;39(1):26–43. doi: 10.1016/s0013-9351(86)80005-6. [DOI] [PubMed] [Google Scholar]
  3. Bowden D. H. Macrophages, dust, and pulmonary diseases. Exp Lung Res. 1987;12(2):89–107. doi: 10.3109/01902148709062834. [DOI] [PubMed] [Google Scholar]
  4. Brown G. M., Donaldson K. Degradation of connective tissue components by lung derived leucocytes in vitro: role of proteases and oxidants. Thorax. 1988 Feb;43(2):132–139. doi: 10.1136/thx.43.2.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bégin R., Rola-Pleszczynski M., Massé S., Lemaire I., Sirois P., Boctor M., Nadeau D., Drapeau G., Bureau M. A. Asbestos-induced lung injury in the sheep model: the initial alveolitis. Environ Res. 1983 Feb;30(1):195–210. doi: 10.1016/0013-9351(83)90180-9. [DOI] [PubMed] [Google Scholar]
  6. Callis A. H., Sohnle P. G., Mandel G. S., Wiessner J., Mandel N. S. Kinetics of inflammatory and fibrotic pulmonary changes in a murine model of silicosis. J Lab Clin Med. 1985 May;105(5):547–553. [PubMed] [Google Scholar]
  7. Chapman H. A., Jr, Stone O. L. Co-operation between plasmin and elastase in elastin degradation by intact murine macrophages. Biochem J. 1984 Sep 15;222(3):721–728. doi: 10.1042/bj2220721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Christner P., Fein A., Goldberg S., Lippmann M., Abrams W., Weinbaum G. Collagenase in the lower respiratory tract of patients with adult respiratory distress syndrome. Am Rev Respir Dis. 1985 May;131(5):690–695. doi: 10.1164/arrd.1985.131.5.690. [DOI] [PubMed] [Google Scholar]
  9. Donaldson K., Bolton R. E., Brown D., Douglas A. An improved macrophage spreading assay--a simple and effective measure of activation. Immunol Commun. 1984;13(3):229–244. doi: 10.3109/08820138409025464. [DOI] [PubMed] [Google Scholar]
  10. Donaldson K., Bolton R. E., Jones A., Brown G. M., Robertson M. D., Slight J., Cowie H., Davis J. M. Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide. Thorax. 1988 Jul;43(7):525–533. doi: 10.1136/thx.43.7.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fantone J. C., Feltner D. E., Brieland J. K., Ward P. A. Phagocytic cell-derived inflammatory mediators and lung disease. Chest. 1987 Mar;91(3):428–435. doi: 10.1378/chest.91.3.428. [DOI] [PubMed] [Google Scholar]
  12. Gadek J. E., Kelman J. A., Fells G., Weinberger S. E., Horwitz A. L., Reynolds H. Y., Fulmer J. D., Crystal R. G. Collagenase in the lower respiratory tract of patients with idiopathic pulmonary fibrosis. N Engl J Med. 1979 Oct 4;301(14):737–742. doi: 10.1056/NEJM197910043011401. [DOI] [PubMed] [Google Scholar]
  13. Gordon S., Werb Z. Secretion of macrophage neutral proteinase is enhanced by colchicine. Proc Natl Acad Sci U S A. 1976 Mar;73(3):872–876. doi: 10.1073/pnas.73.3.872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Holderbaum D., Ehrhart L. A. Substratum influence on collagen and fibronectin biosynthesis by arterial smooth muscle cells in vitro. J Cell Physiol. 1986 Feb;126(2):216–224. doi: 10.1002/jcp.1041260210. [DOI] [PubMed] [Google Scholar]
  15. Hunninghake G. W., Gadek J. E., Kawanami O., Ferrans V. J., Crystal R. G. Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage. Am J Pathol. 1979 Oct;97(1):149–206. [PMC free article] [PubMed] [Google Scholar]
  16. Janoff A. Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis. Am Rev Respir Dis. 1985 Aug;132(2):417–433. doi: 10.1164/arrd.1985.132.2.417. [DOI] [PubMed] [Google Scholar]
  17. Janoff A., White R., Carp H., Harel S., Dearing R., Lee D. Lung injury induced by leukocytic proteases. Am J Pathol. 1979 Oct;97(1):111–136. [PMC free article] [PubMed] [Google Scholar]
  18. Morgan A., Moores S. R., Holmes A., Evans J. C., Evans N. H., Black A. The effect of quartz, administered by intratracheal instillation, on the rat lung. I. The cellular response. Environ Res. 1980 Jun;22(1):1–12. doi: 10.1016/0013-9351(80)90113-9. [DOI] [PubMed] [Google Scholar]
  19. Norris D. A., Clark R. A., Swigart L. M., Huff J. C., Weston W. L., Howell S. E. Fibronectin fragment(s) are chemotactic for human peripheral blood monocytes. J Immunol. 1982 Oct;129(4):1612–1618. [PubMed] [Google Scholar]
  20. Postlethwaite A. E., Kang A. H. Collagen-and collagen peptide-induced chemotaxis of human blood monocytes. J Exp Med. 1976 Jun 1;143(6):1299–1307. doi: 10.1084/jem.143.6.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Reiser K. M., Last J. A. Early cellular events in pulmonary fibrosis. Exp Lung Res. 1986;10(4):331–355. doi: 10.3109/01902148609058286. [DOI] [PubMed] [Google Scholar]
  22. Ruckley V. A., Gauld S. J., Chapman J. S., Davis J. M., Douglas A. N., Fernie J. M., Jacobsen M., Lamb D. Emphysema and dust exposure in a group of coal workers. Am Rev Respir Dis. 1984 Apr;129(4):528–532. [PubMed] [Google Scholar]
  23. Sablonniere B., Scharfman A., Lafitte J. J., Laine A., Aerts C., Hayem A. Enzymatic activities of bronchoalveolar lavages in coal workers pneumoconiosis. Lung. 1983;161(4):219–228. doi: 10.1007/BF02713867. [DOI] [PubMed] [Google Scholar]
  24. Senior R. M., Campbell E. J. Neutral proteinases from human inflammatory cells. A critical review of their role in extracellular matrix degradation. Clin Lab Med. 1983 Dec;3(4):645–666. [PubMed] [Google Scholar]
  25. Shah S. V., Baricos W. H., Basci A. Degradation of human glomerular basement membrane by stimulated neutrophils. Activation of a metalloproteinase(s) by reactive oxygen metabolites. J Clin Invest. 1987 Jan;79(1):25–31. doi: 10.1172/JCI112790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Snider G. L., Lucey E. C., Stone P. J. Animal models of emphysema. Am Rev Respir Dis. 1986 Jan;133(1):149–169. doi: 10.1164/arrd.1986.133.1.149. [DOI] [PubMed] [Google Scholar]
  27. Stankus R. P., Salvaggio J. E. Bronchopulmonary humoral and cellular enhancement in experimental silicosis. J Reticuloendothel Soc. 1981 Feb;29(2):153–161. [PubMed] [Google Scholar]
  28. Sykes S. E., Moores S. R., Jones S. T. Dose-dependent effects in the subacute response of the rat lung to quartz. II. Protease activities and levels of soluble hydroxyproline in lung lavage. Exp Lung Res. 1983 Dec;5(4):245–257. doi: 10.3109/01902148309061518. [DOI] [PubMed] [Google Scholar]
  29. Vracko R. Significance of basal lamina for regeneration of injured lung. Virchows Arch A Pathol Pathol Anat. 1972;355(3):264–274. doi: 10.1007/BF00551062. [DOI] [PubMed] [Google Scholar]
  30. Walton W. H., Dodgson J., Hadden G. G., Jacobsen M. The effect of quartz and other non-coal dusts in coalworkers' pneumoconiosis. Part I: Epidemiological studies. Inhaled Part. 1975 Sep;4(Pt 2):669–690. [PubMed] [Google Scholar]
  31. Werb Z., Gordon S. Secretion of a specific collagenase by stimulated macrophages. J Exp Med. 1975 Aug 1;142(2):346–360. doi: 10.1084/jem.142.2.346. [DOI] [PMC free article] [PubMed] [Google Scholar]

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