Paraquat-induced pulmonary fibrosis. Role of the alveolitis in modulating the development of fibrosis.
Paraquat-induced pulmonary fibrosis. Role of the alveolitis in modulating the development of fibrosis.
复制标题
百草枯诱导的肺纤维化。
DOI：
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发表时间：
1984
期刊：
影响因子：
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通讯作者：
Ronald G. Crystal
中科院分区：
文献类型：
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作者：
C. Schoenberger;S. Rennard;P. B. Bitterman;Yuh Fukuda;V. Ferrans;Ronald G. Crystal
百草枯是一种广泛使用的除草剂，可导致人类和实验动物严重甚至致命的肺纤维化。虽然已知百草枯对肺实质细胞具有直接的细胞毒性，但其导致肺纤维化的机制尚不完全清楚。在百草枯诱导肺纤维化的食食猴模型中，连续2周皮下注射百草枯（10 mg/kg/周）后，暴露动物出现由中性粒细胞和巨噬细胞组成的肺泡炎，通过肺形态学检查和支气管肺泡灌洗进行评估。暴露动物的肺在4至8周内出现典型的间质纤维化。暴露于百草枯后1 - 2周，从暴露于百草枯的动物身上收集的支气管肺泡灌洗液细胞自发释放中性粒细胞的趋化因子，从而为中性粒细胞向肺泡结构募集提供了可能的机制。暴露于百草枯的动物的灌洗液中含有增加的成纤维细胞化学吸引剂纤维连接蛋白（百草枯，3.1 +/- 0.3 ng/微克白蛋白；对照组，1.6 +/- 0.7 ng/微克白蛋白；p < 0.05），这些动物的肺泡巨噬细胞显示纤维连接蛋白的增加，表明局部生产是该糖蛋白增加的部分原因(百草枯，6.1 +/- 2.5 ng/10(6)个细胞/小时；对照组：1.4 +/- 0.5 ng/10(6) cells /h；P < 0.05)。此外，暴露动物的肺泡巨噬细胞自发释放成纤维细胞的生长因子，体外暴露于百草枯的正常肺泡巨噬细胞被诱导释放该生长因子。（摘要删节250字）
Paraquat, a widely used herbicide, can cause severe and often fatal pulmonary fibrosis in humans and in laboratory animals. Although paraquat is known to be directly cytotoxic to lung parenchymal cells, the mechanism by which this leads to pulmonary fibrosis is not completely understood. In a model of paraquat-induced pulmonary fibrosis using the cynomolgus monkey, the administration of paraquat (10 mg/kg/wk subcutaneously for 2 consecutive wk) was followed by an alveolitis comprised of neutrophils and macrophages in the exposed animals as evaluated by lung morphologic examination and bronchoalveolar lavage. The lungs of the exposed animals showed typical interstitial fibrosis within 4 to 8 wk. At 1 to 2 wk after paraquat exposure, bronchoalveolar lavage cells harvested from the paraquat-exposed animals were spontaneously releasing a chemotactic factor for neutrophils, thus providing a possible mechanism for the recruitment of neutrophils to the alveolar structures. Lavage fluid from paraquat-exposed animals contained increased amounts of the fibroblast chemoattractant fibronectin (paraquat, 3.1 +/- 0.3 ng/micrograms albumin; control, 1.6 +/- 0.7 ng/micrograms albumin; p less than 0.05), and alveolar macrophages from these animals showed increased fibronectin production suggesting that local production accounted for part of the increased amounts of this glycoprotein (paraquat, 6.1 +/- 2.5 ng/10(6) cell/h; control, 1.4 +/- 0.5 ng/10(6) cell/h; p less than 0.05). In addition, alveolar macrophages from the exposed animals were spontaneously releasing a growth factor for fibroblasts, and normal alveolar macrophages exposed to paraquat in vitro were induced to release this growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)