Enhanced generation of free radicals from phagocytes induced by mineral dusts.
Enhanced generation of free radicals from phagocytes induced by mineral dusts.
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矿物粉尘诱导的吞噬细胞产生更多的自由基。
DOI：
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发表时间：
1992
影响因子：
6.4
通讯作者：
Nar S. Dalal
中科院分区：
文献类型：
--
作者：
V. Vallyathan;John F. Mega;Xianglin Shi;Nar S. Dalal
一些研究表明，石棉和二氧化硅的肺毒性可能是通过氧化剂诱导的细胞损伤介导的。我们最近报道，表面自由基与新鲜破碎的二氧化硅可能是一个重要的因素，在细胞损伤和诱导肺部疾病。虽然在粉尘-细胞相互作用中氧化自由基的产生已经得到证实，但没有数据将粉尘的毒性与粉尘在与吞噬细胞相互作用期间产生的氧自由基水平相关联。在本研究中，我们已经调查了在体外产生的氧自由基从人中性粒细胞和大鼠肺泡巨噬细胞刺激新鲜破碎的二氧化硅，老化的二氧化硅，铁石棉，青石棉，温石棉，和无毒的灰尘，重晶石。本文用电子自旋共振（ESR）技术，借助自旋捕集剂苯基-N-叔丁基硝酮（PBN），测定了粉尘吞噬过程中产生的氧自由基。相对毒性指数和ESR峰高，在等表面积的基础上，并归一化为重晶石作为一个，表现出直接的关系。标准化毒性指数和峰高分别为：二氧化硅，3.5对2;温石棉，4对2;青石棉，11对8;铁石棉，26对13。添加羟基自由基清除剂，如过氧化氢酶，二甲基亚砜，1，3二甲基-2-硫脲（DMTU），苯甲酸钠，和甘露醇防止自由基的产生。卡莫司汀是一种谷胱甘肽还原酶-谷胱甘肽过氧化物酶抑制剂，导致自由基生成增加5倍。这些结果表明，一种无毒的粉尘，如重晶石，产生的有毒氧自由基在最低水平，可以被正常的细胞防御系统淬灭。对于有毒粉尘，如二氧化硅，铁石棉，温石棉，青石棉，氧自由基生成的潜力是由它们的表面特性，物理尺寸，和基于表面的自由基生成氧化还原位点增强。增强的自由基生成可能损害细胞防御系统，导致细胞损伤。清除剂、螯合剂和增强剂的使用表明基于膜的氧化酶系统可能是自由基产生系统的主要来源。本文提供的数据表明，氧自由基的产生是二氧化硅以及石棉诱导的细胞损伤的重要主要事件。
Several studies have suggested that pulmonary toxicity to asbestos and silica may be mediated through oxidant-induced cell injury. We have reported recently that surface radicals associated with freshly fractured silica may be an important factor in cell injury and induction of pulmonary disease. Although the generation of oxygenated radicals in dust-cell interactions has been demonstrated, there are no data correlating the toxicity of a dust with the level of oxygen radical generation by the dust during its interaction with phagocytic cells. In the present study, we have investigated the in vitro generation of oxygen free radicals from human neutrophils and rat alveolar macrophages stimulated with freshly fractured silica, aged silica, amosite, crocidolite, chrysotile, and nontoxic dust, barite. Electron spin resonance (ESR) with the aid of a spin trap phenyl-N-tert-butyl nitrone (PBN) was used to measure the oxygen radicals generated during phagocytosis of the dusts. The relative toxicity index and ESR peak heights, on an equal surface area basis and normalized to barite as one, showed a direct relationship. The normalized toxicity indices and peak heights were: silica, 3.5 versus 2; chrysotile, 4 versus 2; crocidolite, 11 versus 8; and amosite, 26 versus 13. Addition of hydroxyl radical scavengers such as catalase, dimethyl sulfoxide, 1,3 dimethyl-2-thiourea (DMTU), sodium benzoate, and mannitol prevented the radical generation. Carmustine, a glutathione reductase-glutathione peroxidase inhibitor, caused a 5-fold increase in the radical generation. These results indicate that a nontoxic dust such as barite generates toxic oxygen radicals at a minimal level that can be quenched by the normal cellular defense system. For toxic dusts such as silica, amosite, chrysotile, and crocidolite, the potential for oxygen radical generation is enhanced by their surface properties, physical dimensions, and the surface-based radical-generating redox sites. The enhanced radical generation may impair the cellular defense system, resulting in cell injury. Use of scavengers, chelators, and potentiating agents suggests the membrane-based oxidase system as the probable primary source of the radical-generating system. The data presented herein suggest the generation of oxygen free radicals as an important primary event in silica- as well as asbestos-induced cell injury.
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影响因子：
20.3
作者：
B. Babior
通讯作者：
B. Babior
暴露于石棉状和非纤维颗粒的肺泡巨噬细胞产生超氧化物（O2-）。
影响因子：
11.2
作者：
Hansen,K;Mossman,BT
通讯作者：
Mossman,BT
活性氧代谢物在青石棉石棉对小鼠巨噬细胞毒性中的作用。
影响因子：
11.2
作者：
Goodglick,LA;Kane,AB
通讯作者：
Kane,AB
影响因子：
2.6
作者：
Mossman,BT;Marsh,JP;Shatos,MA;Doherty,J;Gilbert,R;Hill,S
通讯作者：
Hill,S
影响因子：
9.6
作者：
DAVIS, GS
通讯作者：
DAVIS, GS