PERICELLULAR MOBILIZATION OF THE TISSUE-DESTRUCTIVE CYSTEINE PROTEINASES, CATHEPSIN-B, CATHEPSIN-L, AND CATHEPSIN-S, BY HUMAN MONOCYTE-DERIVED MACROPHAGES
PERICELLULAR MOBILIZATION OF THE TISSUE-DESTRUCTIVE CYSTEINE PROTEINASES, CATHEPSIN-B, CATHEPSIN-L, AND CATHEPSIN-S, BY HUMAN MONOCYTE-DERIVED MACROPHAGES
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DOI：
10.1073/pnas.92.9.3849
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发表时间：
1995-04-25
影响因子：
11.1
通讯作者：
WEISS, SJ
中科院分区：
文献类型：
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作者：
REDDY, VY;ZHANG, QY;WEISS, SJ
人巨噬细胞被认为在慢性炎性疾病状态下损害宿主组织，但据报道这些细胞在体外仅表达适度的降解活性。然而，在研究人单核细胞降解细胞外基质组分弹性蛋白的能力时，我们确定了细胞成熟为巨噬细胞群体的培养条件，该巨噬细胞群体显示出比先前归因于任何其他细胞群体的破坏性大数百倍的降解表型。单核细胞衍生的巨噬细胞合成弹性蛋白溶解性基质金属蛋白酶（即，明胶酶B和基质溶解素）以及半胱氨酸蛋白酶（即，组织蛋白酶B、L和S），但通过活体荧光或活性位点标记，在细胞外环境中仅检测到组织蛋白酶作为完全加工的成熟酶。与这些观察结果一致，巨噬细胞介导的弹性蛋白溶解活性不受基质金属蛋白酶抑制剂的影响，但可以通过抑制组织蛋白酶L和S几乎完全消除。这些数据表明，人类巨噬细胞动员半胱氨酸蛋白酶武装自己的一个强大的效应机制，可以参与细胞外基质的病理生理重塑。
Human macrophages are believed to damage host tissues in chronic inflammatory disease states, but these cells have been reported to express only modest degradative activity in vitro. However, while examining the ability of human monocytes to degrade the extracellular matrix component elastin, we identified culture conditions under which the cells matured into a macrophage population that displayed a degradative phenotype hundreds of times more destructive than that previously ascribed to any other cell population. The monocyte-derived macrophages synthesized elastinolytic matrix metalloproteinases (i.e., gelatinase B and matrilysin) as well as cysteine proteinases (i.e., cathepsins B, L, and S), but only the cathepsins were detected in the extracellular milieu as fully processed, mature enzymes by either vital fluorescence or active-site labeling. Consistent with these observations, macrophage-mediated elastinolytic activity was not affected by matrix metalloproteinase inhibitors but could be almost completely abrogated by inhibiting cathepsins L and S. These data demonstrate that human macrophages mobilize cysteine proteinases to arm themselves with a powerful effector mechanism that can participate in the pathophysiologic remodeling of the extracellular matrix.