Immunological factors in the pathogenesis of the hyaline tissue of silicosis.

Abstract

Several hypotheses have been suggested in ex planation of the pathogenesis of silicosis. The earliest was the mechanical hypothesis, according to which, quartz particles, being pointed and sharp, would irritate the cells, stimulating their prolifera tion. This hypothesis was discarded when it was seen that other minerals, with edges even harder and sharper than quartz, such as carborundum and diamond, did not produce fibrosis. In 1922 Gye and Purdy put forward the chemical theory. They sug gested that silicic acid, on being slowly released by crystalline silica, would react as a toxic substance capable of inducing fibrosis. This hypothesis was long held, and until a short time ago it was sup ported and expanded by King (1947) and his colleagues. It was never clearly established how the dissolved silicic acid actually produced fibrosis. It was believed by some that monosilicic acid was the fibrogenic agent, and by others that it was poly merized silicic acid. However, no conclusive evidence has been produced to show that the dissolved silica induces fibrosis and by what means, and this is true also for the interesting hypothesis, recently put forward by Kikuth (1956), which focuses attention on the damage which monomeric silicic acid may exert on some cellular structures (mitochondria). In the last 10 years several physical hypotheses have been proposed: the piezoelectric (Velicogna, 1946; Evans, 1948) and radioactivity of quartz theories (Dantin-Gallego, 1948), both found un acceptable by Parmeggiani (1950), and also the most interesting and impressive hypothesis formulated by J?ger (1954) and Seifert (1954) in which they suggested that the crystalline lattice surface of the quartz would act as a matrix on which cellular proteins would reform and consequently be de natured. The reforming of the proteins would cause them to assume the shape and properties of fibrous proteins, hence the capacity of free crystalline silica for producing fibrous tissue. This theory is sup ported by the fact that amorphous silica is far less fibrogenic than crystalline silica (R?ttner, Willy, and Baumann, 1954). The arguments on the solubility hypothesis and on the hysical hypothesis of the action of surfaces led to numerous additional investigations. In an excellent critical paper, King, Zaidi, and Nagel schmi t (1956) summarized and discussed all the points for and against the theory of solubility. The facts which contradict the validity of this theory as originally stated are the discrepancy between the solubility of various forms of free silica and their fi rogenic action, and the improbability that there is polymerized silicic acid in the tissues. King himself arrived at the conclusion that the solubility of the silica could not serve itself to explain the patho genesis of silicosis. J?ger has ably illustrated the points in favour of the theory of surface action. However, he did not succeed in explaining why certain non-crystalline forms of silica, such as condensation silica (Policard and Co let, 1954), have some fibrogenic action. J?ger also has not explained why areas of massive fibrosis are formed, nor why other mineral dusts alon or in combination with a small percentage of quartz can, in certain conditions, cause massive fibrosis. It must be remembered that the hypotheses of chemical action and surface action were intended more to define the aetiological agent rather than the pathogenic mechanism of silicosis. They state that it is ither dissolved silicic acid or silica crystals as such which cause fibrosis; but how these factors actually induce the formation of this particular hyaline fibrous tissue of silicosis has never been satisfactorily explained. The theory of Holt and Osborne (1953) that polymerized silicic acid acts like mucopolysaccharides, facilitating and directing the formation of fibrils and hence the production of collagen, and the one proposed by J?ger that connective tissue formation would be induced directly by a fibrous transformation of proteins 8