Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1966 Aug 1;124(2):141–154. doi: 10.1084/jem.124.2.141

AN EXAMINATION OF THE CYTOTOXIC EFFECTS OF SILICA ON MACROPHAGES

A C Allison 1, J S Harington 1, M Birbeck 1
PMCID: PMC2180474  PMID: 4288309

Abstract

Effects of silica, diamond dust, and carrageenan on mouse macrophages were studied by phase-contrast cine-micrography, electron microscopy, histochemical techniques for lysosomal enzymes and measurements of the release of lysosomal enzymes into the culture medium. All added materials were rapidly taken up into phagosomes, to which lysosomes became attached. In all cases lysosomal enzymes were discharged into the phagosomes to form secondary lysosomes. Within 24 hr most of the silica particles and enzyme had escaped from the secondary lysosomes and lysosomal enzymes were found in the culture media. Most macrophages were killed by this time. With nontoxic particles (diamond dust, aluminium-coated silica, or silica in the presence of the protective agent polyvinyl-pyridine-N-oxide, PVPNO) ingested particles and lysosomal enzymes were retained within the secondary lysosomes for a much longer time, and cytotoxic effects were considerably delayed or absent altogether. It is concluded that silica particles are toxic because they are efficiently taken up by macrophages and can then react relatively rapidly with the membranes surrounding the secondary lysosomes. The particles and lytic enzymes can then escape into the cytoplasm, producing general damage, and thence into the culture medium. It is suggested that hydrogen bonding of silicic acid with lipid and protein constituents of the membrane accounts for the induced permeability. Protective agents such as PVPNO are retamed in lysosomes and preferentially form hydrogen bonds with silicic acid. Carrageenan is demonstrable within macrophages by its metachromatic reaction. It brings about release of enzymes from secondary lysosomes, but much more slowly than does silica. Silica released from killed macrophages is as cytotoxic as the original preparation. It is suggested that repeated cycles of macrophage killing in vivo leads to the mobilization of fibroblasts and fibrogenesis characterizing the disease silicosis.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALLISON A. C., MALLUCCI L. HISTOCHEMICAL STUDIES OF LYSOSOMES AND LYSOSOMAL ENZYMES IN VIRUS-INFECTED CELL CULTURES. J Exp Med. 1965 Mar 1;121:463–476. doi: 10.1084/jem.121.3.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allison A. C., Magnus I. A., Young M. R. Role of lysosomes and of cell membranes in photosensitization. Nature. 1966 Feb 26;209(5026):874–878. doi: 10.1038/209874a0. [DOI] [PubMed] [Google Scholar]
  3. COHN Z. A., HIRSCH J. G. The isolation and properties of the specific cytoplasmic granules of rabbit polymorphonuclear leucocytes. J Exp Med. 1960 Dec 1;112:983–1004. doi: 10.1084/jem.112.6.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. COHN Z. A., WIENER E. THE PARTICULATE HYDROLASES OF MACROPHAGES. I. COMPARATIVE ENZYMOLOGY, ISOLATION, AND PROPERTIES. J Exp Med. 1963 Dec 1;118:991–1008. doi: 10.1084/jem.118.6.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. COHN Z. A., WIENER E. THE PARTICULATE HYDROLASES OF MACROPHAGES. II. BIOCHEMICAL AND MORPHOLOGICAL RESPONSE TO PARTICLE INGESTION. J Exp Med. 1963 Dec 1;118:1009–1020. doi: 10.1084/jem.118.6.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CURRAN R. C., CLARK A. E. PHAGOCYTOSIS AND FIBROGENESIS IN PERITONEAL IMPLANTS IN THE RAT. J Pathol Bacteriol. 1964 Oct;88:489–502. doi: 10.1002/path.1700880212. [DOI] [PubMed] [Google Scholar]
  7. CURRAN R. C. Observations on the formation of collagen in quartz lesions. J Pathol Bacteriol. 1953 Jul;66(1):271–282. doi: 10.1002/path.1700660131. [DOI] [PubMed] [Google Scholar]
  8. CURRAN R. C., ROWSELL E. V. The application of the diffusion-chamber technique to the study of silicosis. J Pathol Bacteriol. 1958 Oct;76(2):561–568. doi: 10.1002/path.1700760225. [DOI] [PubMed] [Google Scholar]
  9. DALE J. C., KING E. J. Adsorption of dyes, amino acids, proteins, and metal hydroxides on quartz. AMA Arch Ind Hyg Occup Med. 1953 Jun;7(6):484–489. [PubMed] [Google Scholar]
  10. HARINGTON J. S. Some biological actions of silica: their part in the pathogenesis of silicosis. S Afr Med J. 1963 Apr 20;37:451–456. [PubMed] [Google Scholar]
  11. HARRISON C. V., KING E. J., DALE J. C., SICHEL R. The effect of cortisone on experimental silicosis. Br J Ind Med. 1952 Jul;9(3):165–172. doi: 10.1136/oem.9.3.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HOLT S. J. Indigogenic staining methods for esterases. Gen Cytochem Methods. 1958;1:375–398. [PubMed] [Google Scholar]
  13. KARNOVSKY M. J. Simple methods for "staining with lead" at high pH in electron microscopy. J Biophys Biochem Cytol. 1961 Dec;11:729–732. doi: 10.1083/jcb.11.3.729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. KING E. J., HARRISON C. V., ATTYGALLE D. The effect of cortisone on established silicotic fibrosis in the lungs of rats. Br J Ind Med. 1955 Jul;12(3):228–232. doi: 10.1136/oem.12.3.228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MALAWISTA S. E., SEEGMILLER J. E. THE EFFECT OF PRETREATMENT WITH COLCHICINE ON THE INFLAMMATORY RESPONSE TO MICROCRYSTALLINE URATE: A MODEL FOR GOUTY INFLAMMATION. Ann Intern Med. 1965 Apr;62:648–657. doi: 10.7326/0003-4819-62-4-648. [DOI] [PubMed] [Google Scholar]
  16. MARKS J., NAGELSCHMIDT G. Study of the toxicity of dust with use of the in vitro dehydrogenase technique. AMA Arch Ind Health. 1959 Nov;20:383–389. [PubMed] [Google Scholar]
  17. MARKS J. The neutralization of silica toxicity in vitro. Br J Ind Med. 1957 Apr;14(2):81–84. doi: 10.1136/oem.14.2.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. PALADE G. E. A study of fixation for electron microscopy. J Exp Med. 1952 Mar;95(3):285–298. doi: 10.1084/jem.95.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. PEARSON G. R., FREEMAN B. A., HINES W. D. THIN-SECTION ELECTRON MICROGRAPHS OF MONOCYTES INFECTED WITH BRUCELLA SUIS. J Bacteriol. 1963 Nov;86:1123–1125. doi: 10.1128/jb.86.5.1123-1125.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. POLICARD A., COLLET A., PREGERMAIN S. Etude au microscope électronique des modifications infrastructurales présentées par les polynucléaires neutrophiles dans des foyers inflammatoires aseptiques. Rev Hematol. 1959 Apr-Jun;14(2):97–117. [PubMed] [Google Scholar]
  21. RILKE F., KESSEL R. W. HISTOCHEMICAL STUDIES INTO THE CYTOTOXICITY OF TRIDYMITE "IN VITRO". Med Lav. 1963 Mar;54:161–165. [PubMed] [Google Scholar]
  22. Stalder K., Stöber W. Haemolytic activity of suspensions of different silica modifications and inert dusts. Nature. 1965 Aug 21;207(999):874–875. doi: 10.1038/207874a0. [DOI] [PubMed] [Google Scholar]
  23. VIGLIANI E. C., PERNIS B. Immunological aspects of silicosis. Bibl Tuberc. 1963;17:230–279. [PubMed] [Google Scholar]
  24. WEBSTER I., MELAMED M., MUNDAY D. E. The effect of silica particles on esterase and acid phosphatase in macrophages. Med Lav. 1961 Aug-Sep;52:481–486. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES