Role of the alveolar macrophage in lung injury: studies with ultrafine particles.
Role of the alveolar macrophage in lung injury: studies with ultrafine particles.
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DOI：
10.1289/ehp.97-1519541
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发表时间：
1992-07
影响因子：
10.4
通讯作者：
Finkelstein J
中科院分区：
文献类型：
--
作者：
Oberdörster G;Ferin J;Gelein R;Soderholm SC;Finkelstein J
我们进行了一系列的实验与超细颗粒（约20 nm）和较大的颗粒（小于200 nm）的“滋扰”粉尘，以评估参与肺泡巨噬细胞（AM）在颗粒诱导的肺损伤和颗粒易位在大鼠。在肺内滴注超细颗粒和较大颗粒的TiO 2后，我们发现通过肺灌洗参数确定的超细颗粒与大的急性炎症反应相结合的间质访问高度增加。另一项实验显示，肺内滴注吞噬的超细TiO2颗粒（AM内）可防止肺部炎症反应和超细颗粒的间质进入。另一项实验表明，流入肺泡腔的多形核白细胞（PMN）出乎意料地减少了更高剂量的超细颗粒，而肺泡上皮细胞的渗透性（蛋白质渗漏）增加。中性粒细胞流入肺泡腔和肺泡上皮细胞通透性的变化之间的分歧意味着它们是独立的事件。通过肺灌洗分析确定的肺部炎症参数与保留颗粒的表面积相关性最好，而不是与其质量、体积或数量相关。由于较高的剂量导致颗粒的活化分数增加，因此我们认为，由间质空间中的颗粒诱导的炎症事件可以改变肺灌洗可检测到的肺泡空间中的炎症。我们的研究结果证明了AM对改善颗粒诱导的肺损伤的双重作用，即，我们的结论是，超细颗粒的肺毒性增加与其更大的表面积和增加的间质通路有关。（250字处删节）
We conducted a series of experiments with ultrafine particles (approximately 20 nm) and larger particles (less than 200 nm) of "nuisance" dusts to evaluate the involvement of alveolar macrophages (AM) in particle-induced lung injury and particle translocation in rats. After intratracheal instillation of both ultrafine particles and larger particles of TiO2, we found a highly increased interstitial access of the ultrafine particles combined with a large acute inflammatory reaction as determined by lung lavage parameters. An additional experiment revealed that intratracheal instillation of phagocytized ultrafine TiO2 particles (inside AM) prevented both the pulmonary inflammatory reaction and the interstitial access of the ultrafine particles. Another experiment showed that the influx of polymorphonuclear cells (PMN) into the alveolar space unexpectedly decreased with higher doses of ultrafine particles, whereas alveolar epithelial permeability (protein leakage) increased. The divergence between PMN influx into the alveolar space and changes in alveolar epithelial permeability implies that they are separate events. Pulmonary inflammatory parameters determined by lung lavage analysis correlated best with the surface area of the retained particles rather than with their mass, volume, or numbers. Because higher doses resulted in an increased interstitialized fraction of particles, we suggest that inflammatory events induced by particles in the interstitial space can modify the inflammation in the alveolar space detectable by lung lavage. Our results demonstrate the dual role of AM for modifying particle-induced lung injury, i.e., both preventing such injury and contributing to it. We conclude that the increased pulmonary toxicity of ultrafine particles is related to their larger surface area and to their increased interstitial access.(ABSTRACT TRUNCATED AT 250 WORDS)