Starcher B, Williams I
Department of Biochemistry, University of Texas Health Center, Tyler 75710.
Exp Lung Res. 1989 Sep;15(5):785-800. doi: 10.3109/01902148909062861.
Mutant beige mice and normal C57 black mice were given endotoxin intratracheally (IT) once a week for 10 weeks. The objective was to establish whether repeated recruitment of neutrophils to the lung, at levels that induced lung injury to normal mice, would be ineffective in producing lung lesions in neutrophil elastase-deficient beige mice. Endotoxin (25 mg) given IT causes a rapid influx of neutrophils into the lungs of both the C57 black and beige mice, reaching a maximum after 18 h and remaining elevated for at least another 30 h. After 10 weeks of endotoxin instillation the normal C57 black mouse lungs showed evidence of lung injury. There were histological signs of alveolar wall damage, and the mean linear intercepts (Lm) were increased 30% in the endotoxin-treated group. The specific compliance of the lungs from the endotoxin-treated mice was slightly increased. Beige mice, on the other hand, showed no histological or morphological evidence that the neutrophil influx produced lung injury. There was, however, a notable difference in the histological appearance of the control beige lungs compared to control C57 blacks. Beige lungs appeared normal at birth but apparently do not undergo normal alveolarization during neonatal development. Adult lungs have fewer alveoli with smooth terminal air ducts lacking the normal complement of alveolar struts. There was not indication of copper deficiency or problems in elastin synthesis or structure in the beige mice. The results of these studies support a preeminent role for elastase in neutrophil-induced lung lesions.
将突变型米色小鼠和正常的C57黑色小鼠每周经气管内（IT）给予一次内毒素，共10周。目的是确定在对正常小鼠诱导肺损伤的水平下，中性粒细胞反复募集到肺中，对中性粒细胞弹性蛋白酶缺陷的米色小鼠产生肺部病变是否无效。经气管内给予25mg内毒素会导致中性粒细胞迅速流入C57黑色和米色小鼠的肺部，18小时后达到峰值，并至少再持续升高30小时。内毒素滴注10周后，正常的C57黑色小鼠肺部出现肺损伤迹象。有肺泡壁损伤的组织学迹象，内毒素处理组的平均线性截距（Lm）增加了30%。内毒素处理小鼠肺部的比顺应性略有增加。另一方面，米色小鼠没有显示出中性粒细胞流入产生肺损伤的组织学或形态学证据。然而，与对照C57黑色小鼠相比，对照米色小鼠肺部的组织学外观有显著差异。米色小鼠的肺在出生时看起来正常，但在新生儿发育过程中显然没有经历正常的肺泡化。成年肺部的肺泡较少，终末气道光滑，缺乏正常的肺泡支柱。没有迹象表明米色小鼠存在铜缺乏或弹性蛋白合成或结构方面的问题。这些研究结果支持弹性蛋白酶在中性粒细胞诱导的肺部病变中起主要作用。
