Elastase secretion by stimulated macrophages. Characterization and regulation.
Elastase secretion by stimulated macrophages. Characterization and regulation.
复制标题
刺激巨噬细胞的弹性酶分泌。表征和调节。
DOI：
10.1084/jem.142.2.361
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发表时间：
1975-08-01
影响因子：
15.3
通讯作者：
Gordon, S
中科院分区：
文献类型：
--
作者：
Werb, Z;Gordon, S
硫代乙醇酸刺激的小鼠腹膜巨噬细胞分泌一种蛋白水解酶，该酶能降解不溶的弹性蛋白。细胞裂解产物中几乎没有弹性淀粉酶活性，但在无血清培养过程中，大部分酶在细胞外积累。在培养中，弹性酶的分泌持续超过12天，而弹性酶的持续分泌需要蛋白质的合成。未受刺激的巨噬细胞分泌的弹性蛋白酶活性非常低，但可以通过吞噬和细胞内储存乳胶颗粒来触发分泌更高水平的这种酶。巨噬细胞弹性蛋白酶是区别于胰腺和粒细胞弹性蛋白酶的一种独特的酶，也不同于巨噬细胞分泌的其他酶，即胶原酶和纤溶酶原激活剂。巨噬细胞弹性蛋白酶是一种丝氨酸蛋白酶，可被氟化二异丙基磷酸盐、卵子抑制剂、EDTA、二硫苏糖醇和血清抑制。大豆胰酶抑制剂、类火鸡卵粘蛋白和甲苯磺基赖氨酸、苯丙氨酸和乙酰丙氨酸衍生的氯甲基酮对其活性影响不大。不能检测到发色底物中的巨噬细胞弹性蛋白酶对胰腺弹性蛋白酶的降解。受刺激的巨噬细胞分泌的弹性蛋白酶超过原代和已建立的成纤维细胞株。巨噬细胞分泌弹性蛋白酶可能在肺气肿等慢性破坏性肺部疾病的发病机制中起重要作用。
Thioglycolate-stimulated mouse peritoneal macrophages secrete a Proteinase which degrades insoluble elastin. There is little elastase activity in cell lysates but the bulk of the enzyme accumulates extracellularly during culture in serum-free medium. The secretion of elastase is sustained for over 12 days in culture and continued secretion of elastase requires protein synthesis. Unstimulated macrophages secrete very little elastase activity but can be triggered to secrete higher levels of this enzyme by phagocytosis and intracellular storage of latex particles. The macrophages elastase is a distinctive proteinase differing from the elastases of pancreas and granulocytes and is distinct from the other secreted proteinases of macrophages, namely, collagenase and plasminogen activator. The macrophages elastase is a serine proteinase and is inhibited by di- isopropyl phosphoro-fluoridate, ovoinhibitor, EDTA, dithiothretiol, and serum. Its activity is little affected by soybean trypsin inhibitor, turkey ovomucoid and chloromethyl ketones derived from tosyl lysine, tosyl phenylalanine, and acetyltetra alanine. Hydrolysis by macrophage elastase of chromogenic ester substrates for pancreatic elastase could not be detected. Elastase secretion by stimulated macrophages exceeds that by primary and established fibroblast cell strains. It is likely that elastase secretion by macrophages plays a major role in the pathogenesis of chronic destructive pulmonary diseases such as emphysema.