Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages.
Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages.
复制标题
DOI：
--
复制
发表时间：
1993-11
期刊：
影响因子：
--
通讯作者：
S. Shapiro;D. Kobayashi;T. Ley
中科院分区：
文献类型：
--
作者：
S. Shapiro;D. Kobayashi;T. Ley
人肺泡巨噬细胞具有降解弹性蛋白的能力。作为确定负责这种活性的蛋白酶的方法，我们最近克隆了鼠巨噬细胞弹性蛋白酶cDNA，并证明它是基质金属蛋白酶基因家族的成员（Shapiro，S. D、Griffin，G. L.，吉尔伯特，D. J.，詹金斯，N。一、Copeland，N. G.，Welgus，H. G.，西尼尔河M.，和Ley，T. J.（1992）J.Biol.Chem.267，4664-4671）。我们现在报告，有一个人类直系同源的小鼠巨噬细胞金属弹性蛋白酶，我们称之为人类巨噬细胞金属弹性蛋白酶（HME）。全长HME cDNA跨越1.8个酶，并含有1410个碱基对的开放阅读框; HME酶原的预测分子量为54 kDa。人肺泡巨噬细胞中检测到HME mRNA和蛋白。类似于鼠巨噬细胞金属弹性蛋白酶，HME容易经历NH 2-和COOH-末端加工成成熟的22-kDa形式。在大肠杆菌中表达的重组HME和来自人肺泡巨噬细胞条件培养基的天然HME都降解不溶性弹性蛋白。HME是一种独特的人金属蛋白酶，具有弹性蛋白分解活性，并在肺泡巨噬细胞中表达;因此，它是导致以细胞外基质损伤为特征的疾病的候选分子。
Human alveolar macrophages have the capacity to degrade elastin. As an approach to define proteinases responsible for this activity, we recently cloned a murine macrophage elastase cDNA and demonstrated that it is a member of the matrix metalloproteinase gene family (Shapiro, S. D., Griffin, G. L., Gilbert, D. J., Jenkins, N. A., Copeland, N. G., Welgus, H. G., Senior, R. M., and Ley, T. J. (1992) J. Biol. Chem. 267, 4664-4671). We now report that there is a human orthologue of murine macrophage metalloelastase that we call human macrophage metalloelastase (HME). The full-length HME cDNA spans 1.8 kilobases and contains an open reading frame of 1410 base pairs; the predicted molecular mass of the HME proenzyme is 54 kDa. HME mRNA and protein were detected in human alveolar macrophages. Similar to murine macrophage metalloelastase, HME readily undergoes NH2- and COOH-terminal processing to a mature 22-kDa form. Both recombinant HME expressed in Escherichia coli and native HME derived from human alveolar macrophage-conditioned media degraded insoluble elastin. HME is a unique human metalloproteinase that possesses elastolytic activity and is expressed in alveolar macrophages; it is therefore a candidate molecule for the causation of diseases characterized by damage to the extracellular matrix.