The Agonists of Formyl Peptide Receptors Prevent Development of Severe Sepsis after Microbial Infection
The Agonists of Formyl Peptide Receptors Prevent Development of Severe Sepsis after Microbial Infection
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DOI：
10.4049/jimmunol.1001310
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发表时间：
2010-10-01
影响因子：
4.4
通讯作者：
Bae, Yoe-Sik
中科院分区：
文献类型：
--
作者：
Kim, Sang Doo;Kim, Yoon-Keun;Bae, Yoe-Sik
严重脓毒症是重症监护病房死亡的主要原因，当宿主免疫防御无法对抗入侵的微生物时就会发生。在本文中，我们报告了甲酰基肽受体的肽激动剂，包括Trp-Lys-Tyr-Met-Val-D-Met（WKYMVm），通过增强杀菌活性和抑制盲肠结扎穿孔（CLP）脓毒症小鼠模型中重要器官炎症和免疫细胞凋亡来保护免于死亡。施用WKYMVm还增强了CLP小鼠中1型（IFN-γ和IL-12）和17型（IL-17和TGF-β）细胞因子的产生。相比之下，给予WKYMVm抑制CLP小鼠中促炎细胞因子（TNF-α、IL-1 β和IL-6）的产生。WKYMVm的治疗和杀菌作用在IFN-γ缺陷小鼠中部分逆转，而靶器官炎症则没有。同时，WKYMVm的治疗和抗炎作用在IL-17缺陷小鼠中部分逆转。此外，WKYMVm的施用还增强了用LPS加Ag致敏的小鼠中的1型和17型Th细胞应答。这些结果表明，甲酰基肽受体激动剂有效地防止严重脓毒症的微生物感染后的发展，部分通过增强1型和17型免疫应答。免疫学杂志，2010，185：4302-4310。
Severe sepsis, a principal cause of death in intensive care units, occurs when host immune defenses fail to combat invading microbes. In this paper, we report that the administration of peptide agonists of formyl peptide receptors, including Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), protected against death by enhanced bactericidal activity and inhibition of vital organ inflammation and immune cell apoptosis in a cecal ligation and puncture (CLP) sepsis mouse model. The administration of WKYMVm also enhanced the production of type 1 (IFN-gamma and IL-12) and type 17 (IL-17 and TGF-beta) cytokines in CLP mice. In contrast, the administration of WKYMVm inhibited the production of proinflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6) in the CLP mice. The therapeutic and bactericidal effects of WKYMVm were partly reversed in IFN-gamma-deficient mice, whereas target organ inflammation was not. Meanwhile, the therapeutic and anti-inflammatory effects of WKYMVm were partly reversed in IL-17-deficient mice. In addition, the administration of WKYMVm also enhanced type 1 and type 17 Th cell responses in mice sensitized with LPS plus Ags. These results suggest that the agonists of formyl peptide receptors effectively prevent development of severe sepsis following microbial infection partly via augmentation of type 1 and type 17 immune responses. The Journal of Immunology, 2010, 185: 4302-4310.