Mechanisms of mineral dust-induced emphysema
Mechanisms of mineral dust-induced emphysema
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DOI：
10.2307/3433535
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发表时间：
1997-09-01
影响因子：
10.4
通讯作者：
Li, K
中科院分区：
文献类型：
--
作者：
Churg, A;Zay, K;Li, K
矿物粉尘暴露可导致肺气肿和慢性气流阻塞。我们推测，粉尘引起的肺气肿的发病机制类似于香烟烟雾引起的肺气肿，即，从粉尘诱发的炎症细胞的蛋白水解酶的过度释放，和α-1-抗胰蛋白酶（A1 AT）的失活灰尘催化氧化剂的形成。为了验证这一理论，我们研究了A1 AT在体外暴露于石英的抗蛋白水解活性，发现它以剂量-反应方式降低。过氧化氢酶阻止了这种效应，这表明它是由石英产生的过氧化氢介导的。实验还表明，无论是用纯氨基酸还是全蛋白，各种粉尘都能在体外将蛋氨酸氧化为蛋氨酸亚砜。活性大小顺序为煤>石英>二氧化钛。最后，我们使用了一种新的高效液相色谱技术来证明，石英，煤，二氧化钛产生结缔组织破坏大鼠肺，确定的外观锁链素和羟脯氨酸在灌洗液中粉尘滴注后。在颗粒对颗粒的基础上，粉尘效价的顺序与蛋氨酸氧化的顺序相似。结缔组织破坏与灌洗液中多形核白细胞和巨噬细胞的升高有关，目前尚不清楚这些类型的炎性细胞中的一种或两种是否介导了这一过程。这些观察结果支持了我们的理论，即粉尘引起的肺气肿和烟雾引起的肺气肿发生通过类似的机制。
Mineral dust exposure can result in emphysema and chronic airflow obstruction. We postulated that dust-induced emphysema has a pathogenesis similar to that in cigarette smoke-induced emphysema, namely, excess release of proteolytic enzymes from dust-evoked inflammatory cells, and inactivation of alpha-1-antitrypsin (A1AT) by dust-catalyzed formation of oxidants. To test this theory we examined the antiproteolytic activity of A1AT exposed to quartz in vitro and found that it was decreased in a dose-response fashion. Catalase prevented this effect, which suggested that it was mediated by quartz-generated hydrogen peroxide. Wt: also showed that a variety of dusts could oxidize methionine to methionine sulfoxioe in vitro, using either pure amino acid or whole protein. The relative order of activity was coal > quartz > titanium dioxide. Lastly, we used a new high-performance liquid chromatography technique to demonstrate that quartz, coal, and titanium dioxide produced connective tissue breakdown in rat lungs, as determined by the appearance of desmosine and hydroxyproline in lavage fluid after dust instillation. On a particle-for-particle basis, the order of dust potency was similar to that for methionine oxidation. Connective tissue breakdown was associated with elevations of both polymorphonuclear leukocytes and macrophages in lavage fluid, and it is unclear whether one or both of these types of inflammatory cell mediates this process. These observations support our theory that dust-induced emphysema and smoke-induced emphysema occur through similar mechanisms.