VOLUMETRIC LOADING OF ALVEOLAR MACROPHAGES (AM) - A POSSIBLE BASIS FOR DIMINISHED AM-MEDIATED PARTICLE CLEARANCE
VOLUMETRIC LOADING OF ALVEOLAR MACROPHAGES (AM) - A POSSIBLE BASIS FOR DIMINISHED AM-MEDIATED PARTICLE CLEARANCE
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DOI：
10.3109/01902149209020653
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发表时间：
1992-01-01
影响因子：
1.7
通讯作者：
MORROW, PE
中科院分区：
文献类型：
--
作者：
OBERDORSTER, G;FERIN, J;MORROW, PE
本研究以雄性Fischer 344大鼠为对象，为期7个月，采用放射性标记的直径为3.3微米和10.3微米的塑料微球，设置两个剂量水平，通过气管内滴注的方式，旨在验证一种容积性颗粒负荷假说。该假说被提出作为肺部因极低毒性的高度不溶性颗粒而发生粉尘过载情况的一种机制基础，并用于解释肺部颗粒滞留时间的延长。研究采用了气道和深部肺灌洗技术、对处死动物的灌洗细胞和肺进行扫描电子显微镜和光学显微镜检查、肺泡巨噬细胞（AM）内的颗粒分布、放射性颗粒的粪便回收以及通过外部计数测量肺部滞留情况。显微镜评估显示，在滴注后24小时内，基本上所有直径为3.3微米和10.3微米的颗粒都被AM吞噬。一个被吞噬的10.3微米颗粒能够产生假设的使AM实际固定的600立方微米/AM过载标准。假设颗粒在肺部均匀分布，滴注的直径为3.3微米的颗粒数量和体积都不足以产生容积性过载。与3.3微米的颗粒相比，10.3微米的颗粒显然被隔离的程度更大，并且能够极大地延长AM介导的颗粒从肺部区域的清除。小颗粒和大颗粒测量得到的肺部滞留半衰期分别为86 - 109天和870 - 1020天。两种颗粒大小的粪便回收数据与肺部清除数据密切互补。两种颗粒的研究方法被发现支持容积性过载假说。
Using intratracheal instillation of radioactively labeled plastic microspheres of 3.3 and 10.3-mu-m diameter at two dose levels, this 7-month study in male Fischer 344 rats was designed to test a volumetric particulate burden hypothesis that has been proposed as a mechanistic basis for the condition of dust overloading of the lungs with highly insoluble particles of very low toxicity and to explain the prolongation of pulmonary particle retention. The study utilized airway and deep lung lavage techniques, scanning electron and optical microscopy of lavaged cells and lungs of sacrificed animals, particle distribution in alveolar macrophages (AM), fecal recovery of radioactive particles, and lung retention measurements by external counting. Microscopic assessments revealed that essentially all of the 3.3- and 10.3-mu-m-diameter particles were phagocytized by AM within 24 h postinstillation. One phagocytized 10.3-mu-m particle is capable of producing the hypothesized 600-mu-m3/AM overload criterion for virtual AM immobilization. Neither the number nor the volume of 3.3-mu-m-diameter particles instilled was large enough to produce volumetric overloading assuming uniform distribution of the particles in the lung. In contrast to the 3.3-mu-m particles, the 10.3-mu-m particles were apparently sequestered to a greater extent and capable of greatly prolonging AM-mediated clearance of particles from the pulmonary region. The measured pulmonary retention half-times for the small and large particles were 86-109 days and 870-1020 days, respectively. Fecal recovery data closely complemented pulmonary clearance data for both particle sizes. The two-particle approach was found supportive of the volumetric overload hypothesis.