Silicosis and fibrogenesis: fact and artifact.

Although the pulmonary and extrapulmonary manifestations of silicosis in humans have been extensively documented, the mechanisms by which the fibrogenic effects of silica are manifested remain obscure. In this review, both in vitro and in vivo models of silicosis are discussed, with emphasis on the potential methodological pitfalls of each. In animal models, for example, species variability, silica type and route of administration all effect the results obtained. Tissue culture work has provided evidence that the fibroblast-macrophage interaction is a key event in fibrogenesis. However, critical variables in experimental design make it difficult to compare the often conflicting results of different workers. Experimental conditions that directly affect collagen chain biosynthesis and subsequent hydroxylation of proline appear to be of particular importance. It is concluded that, in part because of methodological difficulties, there are insufficient data to draw firm conclusions regarding the effect of silica-exposed macrophages on collagen biosynthesis by fibroblasts in vitro; there are few, if any, data concerning the role of the macrophage that has ingested silica in human or animal models of silicosis.