Mast cells cause apoptosis of cardiomyocytes and proliferation of other intramyocardial cells in vitro
Mast cells cause apoptosis of cardiomyocytes and proliferation of other intramyocardial cells in vitro
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DOI：
10.1161/01.cir.100.13.1443
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发表时间：
1999-09-28
期刊：
影响因子：
37.8
通讯作者：
Sasayama, S
中科院分区：
文献类型：
--
作者：
Hara, M;Matsumori, A;Sasayama, S
背景-肥大细胞是一种多功能细胞，含有多种介质，如细胞因子、蛋白酶和组胺。它们存在于人类心脏中，并与心室肥大和心力衰竭有关。方法和结果：培养的乳鼠心肌细胞与肥大细胞颗粒（MCG）共同孵育24小时，最高浓度的MCG可引起约70%的心肌细胞死亡，电镜和生化指标证实细胞死亡为凋亡。用蛋白酶抑制剂或抗大鼠肥大细胞糜酶1（RMCP 1）中和抗体预处理MCG可阻止MCG介导的细胞毒性，RMCP 1本身可诱导心肌细胞死亡。这些结果表明，MCG中含有的RMCP 1导致心肌细胞死亡，相反，MCG诱导心肌内细胞而不是心肌细胞的增殖。结论肥大细胞通过RMCP 1的活性引起心肌细胞的凋亡和其他心肌细胞的增殖，提示肥大细胞糜酶可能在心力衰竭的发展中起一定作用，心肌细胞的丢失和非心肌细胞的增殖加重了心力衰竭的病理生理过程。
Background-Mast cells are multifunctional cells containing various mediators such as cytokines, proteases, and histamine. They are found in the human heart and have been implicated in ventricular hypertrophy and heart failure. However, their roles in pathogenesis of these diseases are unknown.Methods and Results-Cultured cardiomyocytes from neonatal rats were incubated with mast cell granules (MCGs) for 24 hours, The highest concentration of diluted MCGs caused the death of approximate to 70% of cardiomyocytes, This cell death was proved to be apoptosis, as quantified by electron microscopy and biochemical criteria. MCG-mediated cytotoxicity was prevented by pretreatment of MCGs with protease inhibitors or a neutralizing antibody against rat mast cell chymase 1 (RMCP 1), RMCP 1 by itself was proved to induce cell death of cardiomyocytes. These results suggest that RMCP 1 contained in MCGs causes the death of cardiomyocytes, In contrast, MCGs induced the proliferation of intramyocardial cells other than myocytes. RMCP 1 was also proved to induce their proliferation.Conclusions-Mast cells cause apoptosis of cardiomyocytes and proliferation of other intramyocardial cells via the activity of RMCP 1, Our results suggest that mast cell chymase may play a role in the progression of heart failure, because loss of cardiomyocytes and proliferation of nonmyocardial cells exaggerate its pathophysiology.