MACROPHAGE-ASSOCIATED RESPONSES TO CHRYSOTILE
MACROPHAGE-ASSOCIATED RESPONSES TO CHRYSOTILE
复制标题
DOI：
10.1093/annhyg/38.4.601
复制
发表时间：
1994-08-01
影响因子：
--
通讯作者：
OBERDORSTER, G
中科院分区：
文献类型：
--
作者：
OBERDORSTER, G
不同的肺巨噬细胞（气道巨噬细胞、肺泡巨噬细胞、间质巨噬细胞、血管内巨噬细胞、胸膜巨噬细胞）是肺防御通过吸入沉积的非纤维和纤维颗粒的重要部分。第一道防线是气道巨噬细胞和肺泡巨噬细胞，它们最初与沉积的温石棉纤维相互作用，随后释放出一些介质，包括生长调节和趋化蛋白、花生四烯酸代谢物、蛋白酶、一氧化氮和活性氧，所有这些介质都能影响-也会对-肺中的特定靶细胞产生不利影响。通过粘膜纤毛自动扶梯的机械清除和在肺巨噬细胞吞噬溶酶体的酸性环境中溶解被吞噬的纤维是AM的进一步重要功能。温石棉的毒性似乎更大，或至少具有相同的毒性，以上午作为闪石纤维时，剂量类似的质量管理。然而，根据纤维数量，温石棉对AM的毒性似乎较小。在体外和体内研究中需要考虑适当剂量参数（即纤维质量、数量或表面积）的重要性。短温石棉纤维从大鼠肺中清除的速度非常快，而长温石棉纤维的清除速度则慢得多。这是由于AM对短纤维的有效吞噬作用伴随着在吞噬溶酶体的酸性环境中的溶解。根据大鼠研究的结果预测温石棉在灵长类动物肺中的清除率，得出的总体保留半衰期约为105天，据此预计温石棉在灵长类动物肺中不会发生长期蓄积。在接触温石棉的狒狒中进行的长期吸入研究证实，低稳态肺负荷的快速积累与温石棉约90天的肺滞留半衰期相一致。尽管温石棉的清除速度快，肺部蓄积量低，但在大鼠体内产生的影响，如石棉沉着病，与接触闪石所引起的影响的严重程度相同。在闪石暴露的大鼠，纤维肺负担继续增加与曝光时间。温石棉可能受到透闪石的污染不能解释这些结果，因为在接触温石棉的大鼠体内，纤维的肺部蓄积量并没有增加。在长期的温石棉吸入研究中，由于不会发生累积，因此预计不会出现因肺颗粒物超负荷而产生的影响，而且需要明确区分AM的体积超负荷（温石棉不会发生这种情况）和长纤维的吞噬作用失败或部分吞噬作用。（400字处截断摘要）
The different pulmonary macrophage (airway macrophages, alveolar macrophages, interstitial macrophages, intravascular macrophages, pleural macrophages) are an important part of the lungs' defences against non-fibrous and fibrous particles deposited by inhalation. The first line of defence is airway macrophages and alveolar macrophages (AM) which initially interact with deposited chrysotile fibres and subsequently release a number of mediators including growth regulatory and chemotactic proteins, arachidonic acid metabolites, proteases, NO and active oxygen species, all of which can affect--also adversely--specific target cells in the lung. Mechanical clearance via the mucociliary escalator and dissolution of phagocytized fibres in the acidic milieu of the phagolysosome in pulmonary macrophages are further important functions of AM. Chrysotile appears to be more toxic or at least has the same toxicity to AM as amphibole fibres when doses of a similar mass are administered. However, on a fibre number basis chrysotile appears to be less toxic to AM. The importance of the appropriate dose parameter--ie fibre mass, number or surface area--needs to be considered in in vitro as well as in in vivo studies. Short chrysotile fibres are cleared from rat lungs very rapidly whereas longer ones are cleared at a much slower rate. This is due to efficient phagocytosis of short fibres by AM accompanied by dissolution in the acidic milieu of the phagolysosome. Prediction of chrysotile clearance in primate lung based on results from rat studies result in an overall retention half-time of approximately 105 days, based on which no long-term accumulation of chrysotile in the primate lung is to be expected. Long-term inhalation studies in baboons exposed to chrysotile confirm the very fast build up of a low steady-state lung burden, consistent with a pulmonary retention half-time for chrysotile of approximately 90 days. Despite the fast clearance and low pulmonary accumulation of chrysotile, the resulting effects, such as asbestosis, were found to be of the same severity in rats as those induced by amphibole exposure. In the amphibole-exposed rats, the fibre lung burden continued to increase with exposure time. The potential contamination of chrysotile with tremolite cannot explain these results since there was no increased pulmonary accumulation of fibres in the chrysotile-exposed rats. Effects due to lung particle overload are not to be expected in long-term chrysotile inhalation studies since no accumulation occurs and one needs to distinguish clearly between a volumetric overload of the AM (not occurring with chrysotile) and failed or partial phagocytosis of long fibres.(ABSTRACT TRUNCATED AT 400 WORDS)