PERICELLULAR MOBILIZATION OF THE TISSUE-DESTRUCTIVE CYSTEINE PROTEINASES, CATHEPSIN-B, CATHEPSIN-L, AND CATHEPSIN-S, BY HUMAN MONOCYTE-DERIVED MACROPHAGES

被引:272
作者
REDDY, VY [1 ]
ZHANG, QY [1 ]
WEISS, SJ [1 ]
机构
[1] UNIV MICHIGAN, CTR COMPREHENS CANC, ANN ARBOR, MI 48109 USA
关键词
D O I
10.1073/pnas.92.9.3849
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页码:3849 / 3853
页数:5
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