Mast cell chymase induces apoptosis of vascular smooth muscle cells
Mast cell chymase induces apoptosis of vascular smooth muscle cells
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DOI：
10.1161/01.atv.21.4.516
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发表时间：
2001-04-01
影响因子：
8.7
通讯作者：
Kovanen, PT
中科院分区：
文献类型：
--
作者：
Leskinen, M;Wang, YF;Kovanen, PT
在人冠状动脉粥样硬化中，脱颗粒肥大细胞和凋亡平滑肌细胞（SMC）的数量增加。因此，存在肥大细胞参与调节病变中SMC凋亡的可能性。从大鼠浆膜腔分离的肥大细胞被刺激释放其分泌颗粒。中性蛋白酶糜酶，存在于胞吐颗粒，被发现诱导细胞凋亡时，添加到培养的大鼠主动脉平滑肌细胞。采用流式细胞术、细胞形态学观察、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）法和DNA梯状电泳法检测细胞凋亡。糜酶诱导SMC凋亡的剂量和时间依赖性的方式，其蛋白水解活性是必不可少的促凋亡作用。除大鼠糜酶外，重组人糜酶也能诱导培养的人冠状动脉平滑肌细胞凋亡。提示肥大细胞可能参与了动脉粥样硬化病变中平滑肌细胞的凋亡调控。
In human coronary atheromas, the numbers of degranulated mast cells and of apoptotic smooth muscle cells (SMCs) are increased. Accordingly, the possibility exists that mast cells participate in the regulation of SMC apoptosis in the lesions. Mast cells isolated from the serosal cavities of rats were stimulated to release their secretory granules. The neutral protease chymase, present in the exocytosed granules, was found to induce apoptosis when added to rat aortic SMCs in culture. The chymase-induced apoptosis of SMCs was detected by flow cytometry, microscopic analysis of cellular morphology, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), and electrophoretic demonstration of DNA laddering. Chymase induced SMC apoptosis in a dose- and time-dependent manner, and its proteolytic activity was essential for the proapoptotic effect. In addition to rat chymase, recombinant human chymase was also found to induce apoptosis of human coronary artery SMCs in culture. These results suggest that mast cells may participate in the apoptotic regulation of SMCs in atherosclerotic lesions.