Acid sphingomyelinase inhibition protects mice from lung edema and lethal Staphylococcus aureus sepsis.
Acid sphingomyelinase inhibition protects mice from lung edema and lethal Staphylococcus aureus sepsis.
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DOI：
10.1007/s00109-014-1246-y
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发表时间：
2015-06
影响因子：
4.7
通讯作者：
Grassme, Heike
中科院分区：
文献类型：
--
作者：
Peng, Huiming;Li, Cao;Kadow, Stephanie;Henry, Brian D.;Steinmann, Joerg;Becker, Katrin Anne;Riehle, Andrea;Beckmann, Natalie;Wilker, Barbara;Li, Pin-Lan;Pritts, Timothy;Edwards, Michael J.;Zhang, Yang;Gulbins, Erich;Grassme, Heike
与血管通透性增加相关的肺水肿是金黄色葡萄球菌引起的败血症的严重并发症，也是人类病理和死亡的重要原因。我们研究了哺乳动物酸性鞘磷脂酶 (Asm)/神经酰胺系统在金黄色葡萄球菌引起的肺水肿发展中的作用。我们的研究结果表明，Asm 的遗传缺陷或药物抑制可减轻感染金黄色葡萄球菌的小鼠的肺水肿。 Asm/神经酰胺系统触发超氧化物的形成，导致紧密连接蛋白降解，随后导致肺水肿。用阿米替林（一种 Asm 的有效抑制剂）治疗受感染的小鼠，可以保护小鼠免受金黄色葡萄球菌引起的肺水肿，但并没有减少全身细菌数量。反过来，抗生素治疗减少了细菌数量，但并不能保护小鼠免受肺水肿的影响。相比之下，只有抗生素和阿米替林的组合才能抑制肺水肿和菌血症，保护小鼠免受致命性脓毒症和肺功能障碍的影响，这表明两种药物的组合可以作为脓毒症的新治疗选择。抗生素通常不足以治愈金黄色葡萄球菌引起的败血症。 金黄色葡萄球菌通过 Asm/神经酰胺系统诱导肺水肿。 Asm 遗传缺陷会抑制金黄色葡萄球菌感染后的肺功能障碍。 Asm 的药理抑制可减轻金黄色葡萄球菌引起的肺水肿。抗生素加阿米替林可保护小鼠免受肺水肿和致命的金黄色葡萄球菌败血症的影响。本文的在线版本 (doi:10.1007/s00109-014-1246-y) 包含补充材料，可供授权用户使用。
Pulmonary edema associated with increased vascular permeability is a severe complication of Staphylococcus aureus–induced sepsis and an important cause of human pathology and death. We investigated the role of the mammalian acid sphingomyelinase (Asm)/ceramide system in the development of lung edema caused by S. aureus. Our findings demonstrate that genetic deficiency or pharmacologic inhibition of Asm reduced lung edema in mice infected with S. aureus. The Asm/ceramide system triggered the formation of superoxide, resulting in degradation of tight junction proteins followed by lung edema. Treatment of infected mice with amitriptyline, a potent inhibitor of Asm, protected mice from lung edema caused by S. aureus, but did not reduce systemic bacterial numbers. In turn, treatment with antibiotics reduced bacterial numbers but did not protect mice from lung edema. In contrast, only the combination of antibiotics and amitriptyline inhibited both pulmonary edema and bacteremia protecting mice from lethal sepsis and lung dysfunction suggesting the combination of both drugs as novel treatment option for sepsis. Antibiotics are often insufficient to cure S. aureus–induced sepsis. S. aureus induces lung edema via the Asm/ceramide system. Genetic deficiency of Asm inhibits lung dysfunction upon infection with S. aureus. Pharmacologic inhibition of Asm reduces lung edema induced by S. aureus. Antibiotics plus amitriptyline protect mice from lung edema and lethal S. aureus sepsis. The online version of this article (doi:10.1007/s00109-014-1246-y) contains supplementary material, which is available to authorized users.
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影响因子：
3.1
作者：
McCollister, Bruce D.;Myers, Jesse T.;Vazquez-Torres, Andres
通讯作者：
Vazquez-Torres, Andres
DOI：
10.1099/00221287-6-1-2-95
发表时间：
1952-01-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
DUTHIE, ES;LORENZ, LL
通讯作者：
LORENZ, LL
DOI：
10.1515/bchm3.1994.375.7.447
发表时间：
1994-07-01
期刊：
BIOLOGICAL CHEMISTRY HOPPE-SEYLER
影响因子：
--
作者：
HURWITZ, R;FERLINZ, K;SANDHOFF, K
通讯作者：
SANDHOFF, K
DOI：
10.1006/bbrc.2001.5045
发表时间：
2001-06-22
影响因子：
3.1
作者：
Grassmé, H;Schwarz, H;Gulbins, E
通讯作者：
Gulbins, E
影响因子：
2.3
作者：
Hocke, Andreas C.;Temmesfeld-Wollbrueck, Bettina;Hippenstiel, Stefan
通讯作者：
Hippenstiel, Stefan