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A Novel Anti-Histone H1 Monoclonal Antibody, SSV Monoclonal Antibody, Improves Lung Injury and Survival in a Mouse Model of Lipopolysaccharide-Induced Sepsis-Like Syndrome

机译:一种新的抗组蛋白H1单克隆抗体,SSV单克隆抗体,改善了脂多糖诱导的败血症类综合征的小鼠模型中的肺损伤和存活

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摘要

Background. Histones play important roles in both host defenses and inflammation related to microbial infection. A peptide mimotope (SSV) was identified from a novel histone H1 monoclonal antibody (16G9 mAb) that was shown to inhibit the mixed lymphocyte reaction. In the present study, an anti-SSV producing hybridoma was established. We investigated the effects of SSV mAb in a mouse acute inflammation model induced by intraperitoneal injection of lipopolysaccharide (LPS). Methods. SSV mAb was generated and characterized. Mice were treated with SSV mAb or a control IgG antibody prior to LPS injection. Evaluation of survival rate and lung tissue on histological score was performed. The levels of inflammatory cytokines and histones H1, H3, and H4 in plasma and lung tissue were measured by ELISA. Results. Competitive ELISA revealed that SSV mAb binds to histone H1. SSV mAb improved lung injury and prolonged the survival of LPS-injected mice. Increased levels of histones H1, H3, and H4 and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in plasma and lung tissue after LPS injection were ameliorated by SSV mAb. Conclusion. SSV mAb is shown to have anti-inflammatory activity and organ-protective effects, highlighting the importance of controlling histone H1 as well as H3 and H4 levels during inflammation.
机译:背景。组蛋白在与微生物感染两种宿主防御和炎症中发挥重要作用。肽模拟表位(SSV)是从该显示抑制混合淋巴细胞反应中的新的组蛋白H1单克隆抗体(16G9单抗)识别。在本研究中,抗SSV杂交瘤成立。我们研究了在脂多糖的腹膜内注射(LPS)诱导的小鼠的急性炎症模型SSV mAb的作用。方法。 SSV的mAb产生和表征。小鼠用SSV单抗或之前LPS注射对照IgG抗体处理。进行生存率和组织学评分肺组织的评估。炎性细胞因子和组蛋白H1,H3和H4在血浆和肺组织的水平通过ELISA测量。结果。竞争ELISA透露,SSV单抗结合蛋白H1。 SSV单抗改善肺损伤和延长的LPS注射的小鼠的存活。组蛋白H1,H3和H4以及在LPS注射后血浆和肺组织的炎性细胞因子(TNF-α,IL-1β和IL-6)水平的增加是由SSV单抗改善。结论。 SSV的mAb被示出为具有抗炎活性和器官保护作用,突出炎症期间控制组蛋白H1以及H3和H4水平的重要性。

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