Lugano E M, Dauber J H, Daniele R P
Am J Pathol. 1982 Oct;109(1):27-36.
The acute inflammatory reaction in the lungs of guinea pigs produced by the intratracheal injection of silica was assessed by histologic studies and whole-lung lavage 1, 2, 4, 7, and 14 days after the intratracheal instillation of quartz particles or saline. In addition, lavaged macrophages were cultured in vitro, and the media were assayed for chemotactic factors. This exposure to silica produced a neutrophilic inflammatory response around terminal bronchioles that was well developed within 1 day after injection. Four days after injection, neutrophils were replaced by mononuclear cells; and by 7 days, loosely organized granulomas and collagen deposition were detected in the interstitium. The number of neutrophils (PMNs) recovered by lavage from experimental animals was greatest 1 day after injection and was significantly greater (P less than 0.01) than that for controls at all time points. In contrast, the number of macrophages recovered by lavage did not exceed control levels until 7 days after injection and remained elevated thereafter. Thus, the cells recovered by lavage tended to mirror the changes seen in the inflamed lung. In experiments utilizing blind-well chemotactic chambers, both peritoneal exudate neutrophils and macrophages migrated toward supernatants from cultures of alveolar macrophages lavaged from silica-exposed animals in greater numbers (P less than 0.02) than toward supernatant from control animal macrophage cultures at each time point. Migration of normal alveolar macrophages toward supernatants from all cultures was minimal. Thus, exposure to silica in vivo appears to be a potent stimulus for the release of neutrophil and monocyte chemotactic factors by alveolar macrophages in vitro. The correlation between the types of inflammatory cells identified in the lung both microscopically and by lavage and the chemotactic factors released in vitro by alveolar macrophages from these lungs suggests that alveolar macrophages play a role in mediating pulmonary inflammation in this form of experimental silicosis.
通过组织学研究和全肺灌洗，对气管内注入石英颗粒或生理盐水后1、2、4、7和14天的豚鼠肺部急性炎症反应进行了评估。此外，对灌洗得到的巨噬细胞进行体外培养，并对培养基中的趋化因子进行检测。这种二氧化硅暴露在细支气管末端周围产生了嗜中性炎症反应，注射后1天内反应充分发展。注射后4天，嗜中性粒细胞被单核细胞取代；到7天时，间质中检测到松散组织的肉芽肿和胶原沉积。从实验动物灌洗回收的嗜中性粒细胞（PMN）数量在注射后1天最多，且在所有时间点均显著高于对照组（P小于0.01）。相比之下，灌洗回收的巨噬细胞数量直到注射后7天才超过对照水平，此后一直升高。因此，灌洗回收的细胞倾向于反映炎症肺组织中的变化。在利用盲孔趋化室的实验中，在每个时间点，来自暴露于二氧化硅动物的肺泡巨噬细胞培养上清液吸引的腹膜渗出嗜中性粒细胞和巨噬细胞数量均多于对照动物巨噬细胞培养上清液吸引的数量（P小于0.02）。正常肺泡巨噬细胞向所有培养上清液的迁移极少。因此，体内暴露于二氧化硅似乎是体外肺泡巨噬细胞释放嗜中性粒细胞和单核细胞趋化因子的有力刺激因素。在肺部通过显微镜和灌洗鉴定的炎症细胞类型与这些肺部的肺泡巨噬细胞在体外释放的趋化因子之间的相关性表明，肺泡巨噬细胞在这种实验性矽肺形式的肺部炎症介导中发挥作用。
