Anthrolysin O and other gram-positive cytolysins are toll-like receptor 4 agonists.
Anthrolysin O and other gram-positive cytolysins are toll-like receptor 4 agonists.
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Anthroysin O和其他革兰氏阳性细胞赛蛋白是Toll样受体4激动剂。
DOI：
10.1084/jem.20041215
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发表时间：
2004-12-20
影响因子：
15.3
通讯作者：
Karin, M
中科院分区：
文献类型：
--
作者：
Park, JM;Ng, VH;Maeda, S;Rest, RE;Karin, M
低浓度的炭疽芽孢杆菌致死毒素(LT)可诱导依赖于Toll样受体(TLR)4激活的凋亡反应。当BMDM感染炭疽活菌(Sterne株)时，也观察到类似的TLR4依赖的凋亡反应。然而，TLR4被认为是典型的革兰氏阴性菌产物脂多糖的特异性信号受体，而炭疽杆菌是革兰氏阳性。为了了解炭疽杆菌如何激活TLR4，我们分析了它的培养上清，发现它们含有强大的TLR4刺激活性，也可以诱导巨噬细胞凋亡，其中抗凋亡的p38 MAP激酶(其激活被LF阻止)被抑制。对该活性的纯化表明它是由胆固醇依赖细胞溶素(CDC)家族的成员--花青素O(Alo)组成的。我们发现，重组Alo可以不受内毒素污染的方式激活TLR4，并与LT一起诱导巨噬细胞凋亡。我们还提供了遗传证据，表明Alo是诱导巨噬细胞凋亡所必需的，以应对活的炭疽杆菌感染，并且CDC家族的其他成员也具有激活TLR4的能力。
Exposure of bone marrow–derived macrophages (BMDMs) to low concentrations of Bacillus anthracis lethal toxin (LT), whose catalytic subunit is lethal factor (LF), results in induction of a robust apoptotic response dependent on activation of Toll-like receptor (TLR)4. A similar TLR4-dependent apoptotic response is observed when BMDMs are infected with live B. anthracis (Sterne strain). However, TLR4 is considered to be a specific signaling receptor for lipopolysaccharide (LPS), a typical product of gram-negative bacteria, whereas B. anthracis is gram-positive. To understand how B. anthracis can activate TLR4, we analyzed its culture supernatants and found them to contain a potent TLR4-stimulating activity that can also induce apoptosis in macrophages in which the antiapoptotic p38 MAP kinase (whose activation is prevented by LF) was inhibited. Purification of this activity suggested it consists of anthrolysin O (ALO), a member of the cholesterol-dependent cytolysin (CDC) family. We show that recombinant ALO can activate TLR4 in a manner independent of LPS contamination and, together with LT, can induce macrophage apoptosis. We also provide genetic evidence that ALO is required for induction of macrophage apoptosis in response to infection with live B. anthracis and that other CDC family members share the ability to activate TLR4.
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DOI：
10.1084/jem.175.6.1531
发表时间：
1992-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Harty JT;Bevan MJ
通讯作者：
Bevan MJ
DOI：
10.1073/pnas.90.21.10198
发表时间：
1993-11-01
影响因子：
11.1
作者：
HANNA, PC;ACOSTA, D;COLLIER, RJ
通讯作者：
COLLIER, RJ
DOI：
10.1073/pnas.79.10.3162
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LEPPLA, SH
通讯作者：
LEPPLA, SH
DOI：
10.1073/pnas.96.5.2396
发表时间：
1999-03-02
影响因子：
11.1
作者：
Hersh, D;Monack, DM;Zychlinsky, A
通讯作者：
Zychlinsky, A
影响因子：
15.3
作者：
BOUWER, HGA;NELSON, CS;HINRICHS, DJ
通讯作者：
HINRICHS, DJ