The Effect of Cortisone on Established Silicotic Fibrosis in the Lungs of Rats

King, E. J.; Harrison, C. V.; Attygalle, Daphne

doi:10.1136/oem.12.3.228

Cited by 6 publications

(2 citation statements)

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“…Cortisone and chloroquine are known to stabilize lysosomal membranes and prevent release of lysosomal enzymes under a variety of conditions (41). There is good evidence that cortisone administration diminishes the fibrogenic effects of silica (42,43) although it is without effect on established lesions (44). Inhibition of the proliferative response to silica by chloroquine has also been described (45).…”

Section: Discussionmentioning

confidence: 99%

An Examination of the Cytotoxic Effects of Silica on Macrophages

Allison

Harington

Birbeck

1966

The Journal of Experimental Medicine

809

254

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The fibrogenic effects of silica in man and experimental animals are not yet satisfactorily explained. There is general agreement that in the first instance silica particles deposited in the lung are engulfed by phagocytic cells, which are rapidly destroyed. The cytotoxic effects of silica can be conveniently reproduced in cultures of peritoneal or alveolar macrophages (1), and the relative toxicity of different forms of silica, and of different dusts, on cell cultures agrees with the pathogenicity and fibrogenic potentialities of the dusts in vivo (2, 3).Silica provides, in fact, a remarkable example of selective toxicity for one cell type by a substance of simple chemical composition and low chemical reactivity. Why particles of silica rapidly kill macrophages whereas other particles of comparable size and surface area (such as carbon particles or diamond dust) are ingested by the cells without harmful effects is a problem of academic interest as well as practical importance in relation to the pathogenesis of silicosis.Earlier theories of silica toxicity were reviewed by Nagelschmidt (4) and Harington (5). King in his well known "solubility" theory suggested that silicic acid liberated into the tissues from silica particles brings about the deposition of collagen. Later observations did not support this view, as King himself (6) and Nagelschmidt (4) have pointed out. Curran and Rowsell (7) showed that silica particles implanted into the peritoneum in diffusion chambers do not induce any fibrogenic reaction, although silicic acid is liberated from the chambers. Suggestions have also been made that silica dust might damage macrophages as a result of protein adsorption or denaturation, oxidative changes, or interference with enzyme activity such as that of esterases in the cell. * PreHmlnary accounts of parts of this investigation were presented at a Symposium o n the

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