RESPIRATORY-TRACT RESPONSES TO DUST - RELATIONSHIPS BETWEEN DUST BURDEN, LUNG INJURY, ALVEOLAR MACROPHAGE FIBRONECTIN RELEASE, AND THE DEVELOPMENT OF PULMONARY FIBROSIS
RESPIRATORY-TRACT RESPONSES TO DUST - RELATIONSHIPS BETWEEN DUST BURDEN, LUNG INJURY, ALVEOLAR MACROPHAGE FIBRONECTIN RELEASE, AND THE DEVELOPMENT OF PULMONARY FIBROSIS
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DOI：
10.1016/0041-008x(90)90109-8
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发表时间：
1990-10-01
影响因子：
3.8
通讯作者：
CROSBY, L
中科院分区：
文献类型：
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作者：
DRISCOLL, KE;MAURER, JK;CROSBY, L
采用多学科方法研究呼吸道对二氧化硅（SiO2）或二氧化钛（TiO 2）的反应。大鼠气管内滴注5-100 mg/kg的粉尘和支气管肺泡灌洗液（BALF）的乳酸脱氢酶（LDH）和总蛋白（TP）和离体肺泡巨噬细胞（AM）纤连蛋白释放评估后第7天，14日和28日。在滴注后第1、7和28天测定肺粉尘负荷。这两种粉尘引起BALF LDH和Tp的剂量相关性增加，SiO2的反应更明显和进步。所有剂量的SiO2引起AM纤连蛋白释放的持续增加。TiO 2在≥ 50 mg/kg时刺激AM纤连蛋白释放的持续增加，而在≤ 10 mg/kg时具有短暂或无作用。在所有剂量下观察到SiO2保留增加，而TiO 2保留仅在≥ 100 μ g剂量下增加。50毫克/公斤。在体外暴露的幼稚AM SiO2或TiO 2没有刺激AM纤连蛋白的释放。组织病理学证实在所有SiO2剂量下纤维化;仅TiO 2剂量≥50 mg/kg导致纤维化。这些结果揭示了增加的粉尘滞留、肺损伤激活AM纤连蛋白释放和纤维化发展之间的关联。响应的幅度和时间模式清楚地区分了SiO2和TiO 2。BALF肺损伤标志物和AM纤连蛋白释放增加与纤维化发展的相关性支持使用这些参数作为粉尘诱导的间质性肺病的预测性生物标志物。
A multidisciplinary approach was used to investigate the responses of the respiratory tract to silica (SiO2) or titanium dioxide (TiO2). Rats were intratracheally instilled with 5-100 mg/kg of dust and bronchoalveolar lavage fluid (BALF) lactate dehydrogenase (LDH) and total protein (TP) and ex vivo alveolar macrophage (AM) fibronectin release assessed on Day 7, 14, and 28 after exposure. Lung dust burdens were determined on Days 1,7, and 28 after instillation. Both dusts elicited dose-related increases in BALF LDH and Tp, a response which was more pronounced and progressive with SiO2. All doses of SiO2 elicited persistent increases in AM fibronectin release. TiO2 stimulated persistent increases in AM fibronectin release at .gtoreq.50 mg/kg, with transient or no effect at .ltoreq.10 mg/kg. Increased SiO2 retention was observed for all doses and TiO2 retention was increased only at doses .gtoreq. 50 mg/kg. In vitro exposure of naive AM to SiO2 or TiO2 did not stimulate AM fibronectin release. Histopathology demonstrated fibrosis at all SiO2 doses; only TiO2 doses .gtoreq. 50 mg/kg resulted in fibrosis. These results reveal an association between increased dust retention, lung injury activation of AM fibronectin release, and the development of fibrosis. The magnitude and temporal pattern of responses clearly differentiated SiO2 from TiO2. The correlation fo BALF markers of lung injury and increased AM fibronectin release with the development of fibrosis supports the use of these parameters as predicitve biomarkers of dust-induced interstitial lung disease.