Low expression of CXCR1/2 on neutrophils predicts poor survival in patients with hepatitis B virus-related acute-on-chronic liver failure.
Low expression of CXCR1/2 on neutrophils predicts poor survival in patients with hepatitis B virus-related acute-on-chronic liver failure.
复制标题
中性粒细胞CXCR1/2低表达预示乙型肝炎病毒相关慢加急性肝衰竭患者生存率较差
DOI：
10.1038/srep38714
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发表时间：
2016-12-15
影响因子：
4.6
通讯作者：
Wang FS
中科院分区：
文献类型：
--
作者：
Xu R;Bao C;Huang H;Lin F;Yuan Y;Wang S;Jin L;Yang T;Shi M;Zhang Z;Wang FS
多形核中性粒细胞（PMN）和促炎细胞因子参与了慢加急性肝衰竭（ACLF）的发病机制。但中性粒细胞上CXC趋化因子受体表达作为预测疾病严重程度的生物标志物的效用仍然不确定。在本研究中，我们研究了中性粒细胞上CXCR 1和CXCR 2的动态表达，发现与健康受试者和慢性B型肝炎患者相比，B型肝炎病毒相关的ACLF患者外周血中性粒细胞上CXCR 1和CXCR 2的表达较低。这种表达模式与疾病的严重程度相关。此外，外周血中IL-8产生的增加与CXCR 1和CXCR 2表达的减少显著相关，如用ACLF患者血浆处理中性粒细胞后中性粒细胞上CXCR 1和CXCR 2表达的减少所示。这种作用可以通过用抗IL-8抗体阻断IL-8来克服。我们还发现HBV-ACLF患者肝组织中IL-8产生和中性粒细胞浸润协同增加，这种增加与肝脏炎症有关。总的来说，IL-8的产生增加与中性粒细胞浸润到肝脏和外周中性粒细胞上CXCR 1/2表达减少有关。CXCR 1和CXCR 2表达水平可作为预测ACLF严重程度的早期指标。
Polymorphonuclear neutrophils (PMNs) and proinflammatory cytokines have been implicated in the pathogenesis of acute-on-chronic liver failure (ACLF). But the utility of CXC chemokine receptor expression on PMNs as a biomarker for prediction of disease severity is still uncertain. In this study, we investigated the dynamic expression of CXCR1 and CXCR2 on neutrophils, and found that patients with hepatitis B virus-related ACLF displayed low expression of CXCR1 and CXCR2 on peripheral neutrophils compared with healthy subjects and patients with chronic hepatitis B. This expression pattern was correlated with disease severity. Additionally, increased production of IL-8 in peripheral blood was significantly associated with reduced CXCR1 and CXCR2 expression, as shown by the decreased CXCR1 and CXCR2 expression on neutrophils after treating neutrophils with plasma from ACLF patients. This effect could be overcomed through IL-8 blockage with an anti-IL-8 antibody. We also found that IL-8 production and neutrophil infiltration were coordinately increased in the liver tissue of HBV-ACLF patients, and this increase was associated with liver inflammation. Overall, increased production of IL-8 associated with neutrophils infiltration into the liver and decreased CXCR1/2 expression on peripheral neutrophils. CXCR1 and CXCR2 expression levels could be served as early markers to predict the severity of ACLF.
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