From coal mine dust to quartz: Mechanisms of pulmonary pathogenicity

Exposure to coal mine dust or crystalline silica can result in the initiati on and progression of interstitial lung disease. Pathogenesis is the conseq uence of damage to lung cells and resulting lung scarring associated with a ctivation of fibrotic processes. This review presents the radiologic and hi stologic characteristics of simple and complicated coal workers' pneumoconi osis (CWP) as well as pathological indices of acute and chronic silicosis. This presentation also reviews the results of in vitro, animal, and human i nvestigations that elucidate mechanisms involved in the development of thes e pneumoconioses Results support the involvement of four basic mechanisms i n the etiology of CWP and silicosis: 1. Direct cytotoxicity of coal dust or silica, resulting in lung cell damag e, release of lipases and proteases, and eventual lung scarring. 2. Activation of oxidant production by pulmonary phagocytes, such as alveol ar macrophages. When oxidant production exceeds antioxidant defenses, lipid peroxidation and protein nitrosation occur, resulting in tissue injury and consequent scarring. 3. Activation of mediator release from alveolar macrophages and alveolar ep ithelial cells. Chemokines recruit polymorphonuclear leukocytes and macroph ages from the pulmonary capillaries into the air spaces. Once within the ai r spaces, these leukocytes are activated by proinflammatory cytokines to pr oduce reactive species, which increase oxidant injury and lung scarring. 4. Secretion of growth factors from alveolar macrophages and alveolar epith elial cells. Release of such mediators stimulates fibroblast proliferation and induces fibrosis. In conclusion, results of in vitro and animal studies have provided the bas is for proposing mechanisms that may lead to the initiation and progression of CWP and silicosis. Data obtained from exposed workers has lent support to these proposals. The mechanistic under standing obtained for the develop ment of CWP and silicosis should be useful in elucidating the possible path ogenicity of other inhaled particles.