NEUTROPHIL LYSOSOMAL DYSFUNCTIONS IN MUTANT C57 B1/6J MICE - INTERSTRAIN VARIATIONS IN CONTENT OF LYSOSOMAL ELASTASE, CATHEPSIN-G AND THEIR INHIBITORS
NEUTROPHIL LYSOSOMAL DYSFUNCTIONS IN MUTANT C57 B1/6J MICE - INTERSTRAIN VARIATIONS IN CONTENT OF LYSOSOMAL ELASTASE, CATHEPSIN-G AND THEIR INHIBITORS
复制标题
DOI：
10.1042/bj2990237
复制
发表时间：
1994-04-01
影响因子：
4.1
通讯作者：
LUNGARELLA, G
中科院分区：
文献类型：
--
作者：
GARDI, C;CAVARRA, E;LUNGARELLA, G
在本文中，我们报告了对蛋白酶介导的损伤具有不同易感性的多种小鼠品系的血清抗蛋白酶筛查以及中性粒细胞的生化和功能特征。 C57 B1/6J 小鼠及其突变体紧皮和苍白的血清弹性蛋白酶抑制能力（分别为-30、-65 和-70%）低于其他近交系（即 NMRI 和 Balb/c，两者具有相似的值）。我们证明这些值是弹性蛋白酶的α(1)-蛋白酶抑制剂[PI(E)]浓度降低的结果，PI(E)是弹性蛋白酶和组织蛋白酶G的主要血清抑制剂。此外，分别在皮肤紧绷和苍白的小鼠中观察到中性粒细胞溶酶体功能障碍，其特征是弹性蛋白酶和组织蛋白酶G含量异常高，或溶酶体分泌缺陷。另一种具有溶酶体异常的 C57 B1/6J 突变体是米色小鼠。先前已在该菌株中描述了可忽略量的弹性蛋白酶和组织蛋白酶 G，以及有缺陷的中性粒细胞脱颗粒。然而，我们发现了离散量的潜在形式的中性粒细胞弹性蛋白酶，它通过蛋白酶依赖性机制进行自发激活。我们还报道，该小鼠的中性粒细胞组织蛋白酶 G 与溶酶体膜紧密结合，但在胞吐作用期间以接近正常的量释放。先前报道称胞浆弹性蛋白酶和组织蛋白酶 G 抑制剂对米色中性粒细胞具有特异性，现在在所有检查的菌株中也检测到了这些抑制剂。中性粒细胞功能、溶酶体酶含量和血清抗蛋白酶筛查可能代表蛋白酶-抗蛋白酶平衡中的关键要素，并且可以解释不同种系间对与弹力分解活性有关的病变的不同易感性。
In this paper we report the serum antiprotease screening and the biochemical and functional characteristics of neutrophils in a variety of mouse strains with different susceptibilities for developing a protease-mediated injury. C57 B1/6J mice and their mutants tight-skin and pallid have a lower serum elastase inhibitory capacity (-30, -65 and -70% respectively) than other inbred strains (i.e. NMRI and Balb/c, which both have similar values). We demonstrate that these values are a consequence of a decreased concentration of the alpha(1)-protease inhibitor for elastase [PI(E)], which is the major serum inhibitor of elastase and cathepsin G. In addition, neutrophil lysosomal dysfunctions characterized by abnormally high contents of elastase and cathepsin G, or defective lysosomal secretion are observed in tight-skin and pallid mice respectively. Another C57 B1/6J mutant with lysosomal abnormalities is the beige mouse. Negligible amounts of elastase and cathepsin G, as well as defective neutrophil degranulation, have been described previously in this strain. We found, however, discrete amounts of a latent form of neutrophil elastase that undergoes a spontaneous activation by a protease-dependent mechanism. We also report that neutrophil cathepsin G in this mouse is tightly bound to lysosomal membranes, but is released in near normal quantities during exocytosis. Cytosolic elastase and cathepsin G inhibitors, which were previously reported as being specific for the beige neutrophils, have also been detected in all the examined strains. Neutrophil functions, lysosomal enzyme content and serum antiprotease screening may represent key elements in the protease-antiprotease balance and may explain the different interstrain susceptibility to developing lesions in which an elastolytic activity has been implicated.