Carrero Javier A, Calderon Boris, Unanue Emil R
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Immunol. 2004 Apr 15;172(8):4866-74. doi: 10.4049/jimmunol.172.8.4866.
Infection of mice with Listeria monocytogenes caused marked lymphocyte apoptosis in the white pulp of the spleen on day 2 postinfection. We prove in this study that listeriolysin O (LLO), a pore-forming molecule and a major virulence factor of Listeria, could directly induce murine lymphocyte apoptosis both in vivo and in vitro at nanomolar and subnanomolar doses. Induction of apoptosis by LLO was rapid, with caspase activation seen as early as 30 min post-treatment. T cells lost their mitochondrial membrane potential and exposed phosphatidylserine within 8 h of treatment. Incubation of lymphocytes with a pan-caspase inhibitor blocked DNA laddering and caspase-3 activation, but did not block phosphatidylserine exposure or loss of mitochondrial membrane potential. We describe a novel function for LLO: induction of lymphocyte apoptosis with rapid kinetics, effected by both caspase-dependent and -independent pathways.
用单核细胞增生李斯特菌感染小鼠后，在感染后第2天，脾脏白髓中出现明显的淋巴细胞凋亡。我们在本研究中证明，李斯特菌溶素O（LLO）是一种成孔分子，也是李斯特菌的主要毒力因子，在纳摩尔和亚纳摩尔剂量下，它能在体内和体外直接诱导小鼠淋巴细胞凋亡。LLO诱导凋亡的速度很快，早在处理后30分钟就可见半胱天冬酶激活。T细胞在处理后8小时内失去线粒体膜电位并暴露磷脂酰丝氨酸。用泛半胱天冬酶抑制剂孵育淋巴细胞可阻断DNA梯状条带形成和半胱天冬酶-3激活，但不阻断磷脂酰丝氨酸暴露或线粒体膜电位丧失。我们描述了LLO的一种新功能：通过半胱天冬酶依赖性和非依赖性途径快速诱导淋巴细胞凋亡。
