Biochemical and cellular mechanisms of dust-induced lung fibrosis

The sequence of cellular and biochemical events in response to the deposition of dust particles in lung tissue is described. Primary reactions at the lung surface include changes in the free cell population, the alveolar surface protein and in the quantity of pulmonary surfactant, a lipoprotein-rich material secreted by Type II cells. The relationship between these changes and lung fibrogenesis is discussed. It is suggested that such primary changes are protective mechanisms which may assist in the prevention of fibrogenesis rather than lead to an increase in collagen formation and deposition. If these primary defenses are overcome, then the interstitial fibroblastlike cell may have a prominent role in fibrogenesis. Therefore detailed observations of the interaction between lung fibroblasts and mineral dusts in vitro are described. As fibrogenesis may be arrested in vivo, or possibly reversed, and does not always progress to fibrosis, final consideration is given to the step from fibrogenesis to fibrosis. It is suggested that this step may involve other tissue proteins apart from collagen and that the irreversible nature of fibrosis can be explained by the formation of strong intermolecular crosslinks between different proteins. The types of crosslinks that may be involved are discussed. Emphasis is placed on the role of calcium-dependent transglutaminases in fibrosis, as these enzymes have hitherto received little attention.