Hereditary emphysema in the tight-skin mouse. Evaluation of pathogenesis.
Hereditary emphysema in the tight-skin mouse. Evaluation of pathogenesis.
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皮肤紧绷的小鼠患有遗传性肺气肿。
DOI：
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
R. Crystal
中科院分区：
文献类型：
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作者：
G. Rossi;G. Hunninghake;J. Gadek;S. Szapiel;O. Kawanami;V. Ferrans;R. Crystal
紧皮（Tsk/+）小鼠是一种遗传决定的模型，其特征在于肺泡扩大和肺气肿的生理学证据。这些动物的肺形态学评价表明，在肺气肿病变发生前，下呼吸道中潜在的蛋白酶分泌细胞（肺泡巨噬细胞和中性粒细胞）数量增加。通过支气管肺泡灌洗对这些动物肺部的中性粒细胞进行定量。在Tsk/+小鼠中，中性粒细胞占所有炎性和免疫效应细胞的3.5 +/- 2%，而对照（+/+）小鼠中为0.4 +/- 0.1%（p <0.01）。Tsk/+动物没有感染的证据来解释中性粒细胞的存在，并且肺T-和B-淋巴细胞的比例正常，表明它们的肺免疫学正常。没有证据表明Tsk/+小鼠存在抗蛋白酶缺陷; Tsk/+小鼠血清抑制中性粒细胞弹性蛋白酶的能力与对照+/+动物无差异。然而，事实上，这些动物有一个持续的低水平的巨噬细胞-中性粒细胞肺泡炎的肺气肿病变的发展之前，意味着肺破坏可能是相关的，在某种程度上，与慢性蛋白酶-抗蛋白酶失衡，类似于人类肺气肿的假设。
The tight-skin (Tsk/+) mouse is a genetically determined model characterized by alveolar enlargement and physiologic evidence of emphysema. Morphologic evaluation of the lungs of these animals demonstrated increased numbers of potential protease-secreting cells (alveolar macrophages and neutrophils) in the lower respiratory tract prior to development of the emphysematous lesions. Quantitation of the neutrophils in the lungs of these animals was carried out by bronchoalveolar lavage. In the Tsk/+ mice, neutrophils constituted 3.5 +/- 2% of all inflammatory and immune effector cells present compared with 0.4 +/- 0.1% in control (+/+) mice (p less than 0.01). The Tsk/+ animals had no evidence of infection to explain the presence of the neutrophils and had normal proportions of lung T- and B-lymphocytes, suggesting that their lungs were immunologically normal. There was no evidence that the Tsk/+ mice have an antiprotease deficit; the capacity of serum of Tsk/+ mice to inhibit neutrophil elastase was no different from that of control +/+ animals. However, the fact that these animals have a persistent low level macrophage-neutrophil alveolitis prior to the development of the emphysematous lesion implies that the lung destruction may be associated, in part, with a chronic protease-antiprotease imbalance, similar to that hypothesized for human emphysema.