The Essential Role of Lipopolysaccharide-Binding Protein in Protection of Mice Against a Peritoneal Salmonella Infection Involves the Rapid Induction of an Inflammatory Response1
The Essential Role of Lipopolysaccharide-Binding Protein in Protection of Mice Against a Peritoneal Salmonella Infection Involves the Rapid Induction of an Inflammatory Response1
复制标题
脂多糖结合蛋白在保护小鼠免受腹膜沙门氏菌感染方面的重要作用涉及快速诱导炎症反应1
作者：
J. Heinrich;M. Bernheiden;Gabriela Minigo;K. Yang;C. Schütt;D. Männel;R. Jack
急性和慢性过度炎症是主要的临床关注点，因此许多治疗策略针对灭活炎症系统的部分。然而，生存取决于对病原体攻击的快速反应，由于适应性免疫系统需要几天才能充分反应，我们最初依赖于一系列先天防御，其中许多是通过激活炎症网络的部分来运作的。例如，LPS结合蛋白（LBP）可以将革兰氏阴性菌的LPS转移到巨噬细胞表面的CD 14上，这引发了炎症反应。然而，这一系列事件在感染中的重要性尚不清楚。首先，先天系统是多余的，细菌有许多成分可以作为它的靶点;其次，LBP可以将LPS转移到其他不诱导炎症的受体。在这项研究中，我们表明，先天防御致命的腹膜感染沙门氏菌需要直接的促炎参与的LBP，这是一个主要的非冗余功能的LBP在这种感染模型。这强调了阻断LBP引发的炎症级联反应会使一个重要的防御途径失效。任何可能实现的抗炎保护都必须与使先天系统对革兰氏阴性病原体的存在视而不见的固有风险相平衡。
Acute and chronic hyperinflammation are of major clinical concern, and many treatment strategies are therefore directed to inactivating parts of the inflammatory system. However, survival depends on responding quickly to pathogen attack, and since the adaptive immune system requires several days to adequately react, we rely initially on a range of innate defenses, many of which operate by activating parts of the inflammatory network. For example, LPS-binding protein (LBP) can transfer the LPS of Gram-negative bacteria to CD14 on the surface of macrophages, and this initiates an inflammatory reaction. However, the importance of this chain of events in infection is unclear. First, the innate system is redundant, and bacteria have many components that may serve as targets for it. Second, LBP can transfer LPS to other acceptors that do not induce inflammation. In this study, we show that innate defense against a lethal peritoneal infection with Salmonella requires a direct proinflammatory involvement of LBP, and that this is a major nonredundant function of LBP in this infection model. This emphasizes that blocking the LBP-initiated inflammatory cascade disables an essential defense pathway. Any anti-inflammatory protection that may be achieved must be balanced against the risks inherent in blinding the innate system to the presence of Gram-negative pathogens.
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DOI：
10.1016/0167-5699(92)90198-g
发表时间：
1992-01-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
JANEWAY, CA
通讯作者：
JANEWAY, CA
影响因子：
56.9
作者：
SCHUMANN, RR;LEONG, SR;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
56.9
作者：
WRIGHT, SD;RAMOS, RA;MATHISON, JC
通讯作者：
MATHISON, JC
DOI：
10.1073/pnas.96.25.14459
发表时间：
1999-12-07
影响因子：
11.1
作者：
Underhill, DM;Ozinsky, A;Aderem, A
通讯作者：
Aderem, A
影响因子：
15.9
作者：
Yu, B;Hailman, E;Wright, SD
通讯作者：
Wright, SD