αDβ2 as a novel target of experimental polymicrobial sepsis.
αDβ2 as a novel target of experimental polymicrobial sepsis.
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DOI：
10.3389/fimmu.2022.1059996
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
自三十年前定义脓毒症以来，它一直是深入研究的目标。然而，脓毒症的死亡率和发病率很高，没有特异性的治疗方法。αDβ2（CD 11 d/CD 18）是β2整合素的四个成员之一。其在脓毒症中的作用研究有限。利用实验性多微生物脓毒症模型，我们发现αDβ2缺陷与肺损伤较少和预后较好相关，这与其他β2整合素成员αLβ2（CD 11 a/CD 18）和αMβ2（CD 11b/CD 18）形成鲜明对比。αDβ2基因敲除小鼠中细菌载量的减少支持了这种表型。进一步分析表明，αDβ2缺乏导致小鼠和人体系统中中性粒细胞死亡减少以及中性粒细胞吞噬作用增加。我们的数据显示，在β2整合素成员中，αDβ2具有独特的作用，这将作为改善脓毒症结局的潜在靶点。
Since sepsis was defined three decades ago, it has been a target of intensive study. However, there is no specific sepsis treatment available, with its high mortality and morbidity. αDβ2 (CD11d/CD18) is one of the four β2 integrin members. Its role in sepsis has been limitedly studied. Using an experimental polymicrobial sepsis model, we found that the deficiency of αDβ2 was associated with less lung injury and better outcome, which was in sharp contrast to other β2 integrin member αLβ2 (CD11a/CD18), and αMβ2 (CD11b/CD18). This phenotype was supported by a reduction of bacterial loads in αDβ2 knockout mice. Further analysis showed that the deficiency of αDβ2 led to a reduction of neutrophil cell death as well as an increase in neutrophil phagocytosis in both murine and human systems. Our data showed a unique role of αDβ2 among the β2 integrin members, which would serve as a potential target to improve the outcome of sepsis.