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首页> 外文期刊>The FEBS journal >Circulating BiP/Grp78 is a novel prognostic marker for sepsis-mediated immune cell death
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Circulating BiP/Grp78 is a novel prognostic marker for sepsis-mediated immune cell death

机译：循环BIP / GRP78是一种用于败血症介导的免疫细胞死亡的新型预后标志物

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Sepsis remains to be a major contributor to mortality in ICUs, and immune suppression caused by immune cell apoptosis determines the overall patient survival. However, diagnosis of sepsis-induced lymphopenia remains problematic with no accurate prognostic techniques or biomarkers for cell death available. Developing reliable prognostic tools for sepsis-mediated cell death is not only important for identifying patients at increased risk of immune suppression but also to monitor treatment progress of currently trialed immunotherapy strategies. We have previously shown an important role for endoplasmic reticulum stress (ER stress) in inducing sepsis-mediated cell death and here report on the identification of a secreted form of the ER chaperone BiP (immunoglobulin binding protein) as a novel circulating prognostic biomarker for immune cell death and ER stress during sepsis. Using biochemical purification and mass spectrometry coupled with an establishedin vitrosepsis cell death assay, we identified BiP/Grp78 as a factor secreted by lipopolysaccharide-activated macrophages that is capable of inducing cell death in target cells. Quantitative ELISA analysis showed significantly elevated levels of circulating BiP in mice undergoing polymicrobial sepsis, which was absent inBim(-/-)mice that are protected from sepsis-induced lymphopenia. Using blood serum from human sepsis patients, we could detect a significant difference in levels of secreted BiP in sepsis patients compared to nonseptic controls, suggesting that secreted circulating BiP could indeed be used as a prognostic marker that is directly correlative to immune cell death during sepsis.
机译：脓毒症仍然是ICU死亡率的主要原因，而免疫细胞凋亡引起的免疫抑制决定了患者的总体存活率。然而，由于没有准确的预后技术或细胞死亡生物标志物，脓毒症诱导的淋巴细胞减少症的诊断仍然存在问题。为脓毒症介导的细胞死亡开发可靠的预后工具不仅对识别免疫抑制风险增加的患者很重要，而且对监测目前试验性免疫治疗策略的治疗进展也很重要。我们之前已经证明内质网应激（ER应激）在诱导脓毒症介导的细胞死亡中起着重要作用，本文报告了一种分泌型ER伴侣BiP（免疫球蛋白结合蛋白）作为脓毒症期间免疫细胞死亡和ER应激的新循环预后生物标记物的鉴定。通过生化纯化和质谱分析，结合已建立的vitrosepsis细胞死亡分析，我们确定BiP/Grp78是一种由脂多糖激活的巨噬细胞分泌的因子，能够诱导靶细胞中的细胞死亡。定量ELISA分析显示，在经历多微生物败血症的小鼠中，循环BiP水平显著升高，这在受败血症诱导的淋巴细胞减少保护的IM（-/-）小鼠中是不存在的。使用人类脓毒症患者的血清，我们可以检测到脓毒症患者与非脓毒症对照组相比分泌性BiP水平的显著差异，这表明分泌性循环BiP确实可以用作与脓毒症期间免疫细胞死亡直接相关的预后标志物。

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