Castranova V
a Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , West Virginia , USA.
Inhal Toxicol. 2000 Jan;12 Suppl 3:7-14. doi: 10.1080/08958378.2000.11463226.
Exposure to coal mine dust or crystalline silica can result in the initiation and progression of interstitial lung disease. Pathogenesis is the consequence of damage to lung cells and resulting lung scarring associated with activation of fibrotic processes. This review presents the radiologic and histologic characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathological indices of acute and chronic silicosis. This presentation also reviews the results of in vitro, animal, and human investigations that elucidate mechanisms involved in the development of these pneumoconioses. Results support the involvement of four basic mechanisms in the etiology of CWP and silicosis: 1. Direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring. 2. Activation of oxidant production by pulmonary phagocytes, such as alveolar 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 epithelial cells. Chemokines recruit polymorphonuclear leukocytes and macrophages from the pulmonary capillaries into the air spaces. Once within the air spaces, these leukocytes are activated by proinflammatory cytokines to produce reactive species, which increase oxidant injury and lung scarring. 4. Secretion of growth factors from alveolar macrophages and alveolar epithelial cells. Release of such mediators stimulates fibroblast proliferation and induces fibrosis. In conclusion, results of in vitro and animal studies have provided the basis 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 understanding obtained for the development of CWP and silicosis should be useful in elucidating the possible pathogenicity of other inhaled particles.
接触煤矿粉尘或结晶硅石可导致间质性肺病的发生和发展。发病机制是肺细胞受损以及由此导致的与纤维化过程激活相关的肺瘢痕形成的结果。本综述介绍了单纯性和复杂性煤工尘肺（CWP）的放射学和组织学特征以及急性和慢性矽肺的病理指标。本报告还回顾了体外、动物和人体研究的结果，这些研究阐明了这些尘肺病发展过程中涉及的机制。结果支持CWP和矽肺病因中涉及四种基本机制：1. 煤尘或硅石的直接细胞毒性，导致肺细胞损伤、脂肪酶和蛋白酶释放，最终形成肺瘢痕。2. 肺吞噬细胞（如肺泡巨噬细胞）激活氧化剂产生过程中。当氧化剂产生超过抗氧化防御能力时，就会发生脂质过氧化和蛋白质亚硝化，导致组织损伤并进而形成瘢痕组织。3. 激活肺泡巨噬细胞和肺泡上皮细胞释放介质。趋化因子将多形核白细胞和巨噬细胞从肺毛细血管招募到气腔中这些白细胞一旦进入气腔，就会被促炎细胞因子激活，产生活性物质，增加氧化损伤和肺瘢痕形成。4肺泡巨噬细胞和肺泡上皮细胞分泌生长因子。这些介质释放会刺激成纤维细胞增殖并诱导纤维化形成。总之，体外和动物研究结果为提出可能导致CWP和矽肺发生和发展的机制提供了依据。从接触工人那里获得的数据支持了这些观点。对CWP和矽肺发展过程的机制理解应有助于阐明其他吸入颗粒的可能致病性。
