Massari P, Ho Y, Wetzler L M
Evans Biomedical Research Center, 650 Albany Street, Boston University School of Medicine, Boston Medical Center, Boston, MA 02118, USA.
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9070-5. doi: 10.1073/pnas.97.16.9070.
Neisserial porins are strong immune adjuvants and B cell activators. The effect of neisserial porin PorB on activation-induced cell death was investigated, as a potential additional mechanism of the porin's immunopotentiating ability. Neisserial porins interact with target cells to localize intracellularly in the mitochondrial compartment without negatively affecting cellular survival. Pretreatment with Neisseria meningitidis PorB porin decreased or abrogated the mitochondrial damage induced by apoptotic stimuli. In addition, end stage determinants of apoptosis, including DNA breakdown, were diminished by PorB. Immunoprecipitation experiments revealed that PorB interacts with the mitochondrial porin VDAC (voltage-dependent anion channel). The mechanism of the antiapoptotic effect of neisserial porins could be explained by the protein-protein interaction of PorB with VDAC, similar to the interaction of VDAC with antiapoptotic Bcl-2 proteins, resulting in an enhancement of cell survival and continued activation of B cells.
奈瑟菌孔蛋白是强大的免疫佐剂和B细胞激活剂。研究了奈瑟菌孔蛋白PorB对激活诱导的细胞死亡的影响,将其作为孔蛋白免疫增强能力的一种潜在附加机制。奈瑟菌孔蛋白与靶细胞相互作用,定位于线粒体内的细胞内区域,而不会对细胞存活产生负面影响。用脑膜炎奈瑟菌PorB孔蛋白预处理可减少或消除凋亡刺激诱导的线粒体损伤。此外,PorB可减少包括DNA断裂在内的凋亡终末期决定因素。免疫沉淀实验表明,PorB与线粒体孔蛋白VDAC(电压依赖性阴离子通道)相互作用。奈瑟菌孔蛋白的抗凋亡作用机制可以通过PorB与VDAC的蛋白质-蛋白质相互作用来解释,类似于VDAC与抗凋亡Bcl-2蛋白的相互作用,从而提高细胞存活率并持续激活B细胞。