Kuo C F, Wu J J, Tsai P J, Kao F J, Lei H Y, Lin M T, Lin Y S
Department of Microbiology, National Cheng Kung University Medical College, Taiwan, Republic of China.
Infect Immun. 1999 Jan;67(1):126-30. doi: 10.1128/IAI.67.1.126-130.1999.
Treatment of U937 human monocyte-like cells with Streptococcus pyogenes led to an induction of apoptosis in these cells. A comparison between the wild-type strain and its isogenic protease-negative mutant indicated that the production of streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease, caused a greater extent of apoptosis in U937 cells. Further study using purified SPE B showed that this protease alone could induce U937 cells to undergo apoptosis, which was characterized by morphologic changes, DNA fragmentation laddering on the gel, and an increase in the percentages of hypodiploid cells. The protease activity of SPE B was required for apoptosis to proceed, since treatment with cysteine protease inhibitor E64 or heat inactivation abrogated this death-inducing effect. The SPE B-induced apoptosis pathway was interleukin-1beta converting enzyme (ICE) family protease dependent. Further experiments showed that the phagocytic activity of U937 cells was reduced by SPE B. Treatment with E64 and heat inactivation both abrogated this phagocytosis-inhibitory effect. Taken together, the present data show that SPE B not only possesses the ability to induce apoptosis in monocytic cells but also helps bacteria to resist phagocytosis by host cells.
用化脓性链球菌处理人U937单核细胞样细胞会导致这些细胞发生凋亡。野生型菌株与其同基因蛋白酶阴性突变体之间的比较表明，半胱氨酸蛋白酶——链球菌致热外毒素B（SPE B）的产生，在U937细胞中引起了更大程度的凋亡。使用纯化的SPE B进行的进一步研究表明，仅这种蛋白酶就能诱导U937细胞发生凋亡，其特征为形态学变化、凝胶上DNA梯状条带的出现以及亚二倍体细胞百分比的增加。凋亡的发生需要SPE B的蛋白酶活性，因为用半胱氨酸蛋白酶抑制剂E64处理或热灭活会消除这种诱导死亡的效应。SPE B诱导的凋亡途径依赖于白细胞介素-1β转换酶（ICE）家族蛋白酶。进一步的实验表明，SPE B会降低U937细胞的吞噬活性。用E64处理和热灭活都消除了这种吞噬抑制作用。综上所述，目前的数据表明，SPE B不仅具有在单核细胞中诱导凋亡的能力，还能帮助细菌抵抗宿主细胞的吞噬作用。
