title: Minerals, fibrosis, and the lung.
abstract: Determinants of pulmonary fibrosis induced by inhaled mineral dusts include quantity retained, particle size, and surface area, together with their physical form and the reactive surface groups presented to alveolar cells. The outstanding problem is to ascertain how these factors exert their deleterious effects. Both compact and fibrous minerals inflict membrane damage, for which chemical mechanisms still leave uncertainty. A major weakness of cytotoxicity studies, even when lipid peroxidation and reactive oxygen species are considered, lies in tacitly assuming that membrane damage suffices to account for fibrogenesis, whereas the parallel occurrence of such manifestations does not necessarily imply causation. The two-phase procedure established that particles, both compact and fibrous, induce release of a macrophage factor that provokes fibroblasts into collagen synthesis. The amino acid composition of the macrophage fibrogenic factor was characterized and its intracellular action explained. Fibrous particles introduce complexities respecting type, durability, and dimensions. Asbestotic fibrosis is believed to depend on long fibers, but scrutiny of the evidence from experimental and human sources reveals that a role for short fibers needs to be entertained. Using the two-phase system, short fibers proved fibrogenic. Other mechanisms, agonistic and antagonistic, may participate. Growth factors may affect the fibroblast population and collagen production, with cytokines such as interleukin-1 and tumor necrosis factor exerting control. Immune involvement is best regarded as an epiphenomenon. Downregulation of fibrogenesis may follow collagenase release from macrophages and fibroblasts, while augmented type II cell secretion of lipid can interfere with the macrophage-particle reaction.
authors.affiliation: Institute of Occupational Medicine, Edinburgh, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Heppleston
mesh_terms: D000818:Animals; D003032:Coal Mining; D003094:Collagen / Q000096:biosynthesis; D003238:Connective Tissue / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects; D050356:Lipid Metabolism; D008264:Macrophages / Q000187:drug effects; D008903:Minerals / Q000009:adverse effects*; D009784:Occupational Diseases / Q000209:etiology; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000276:immunology
chemical_list: D008903:Minerals; D003094:Collagen