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Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis

Cellular & Molecular Immunology volume 13, pages 103–109 (2016)Cite this article

Abstract

Complement 5a (C5a) has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors (C5aRs; C5aR and C5L2) as biomarkers for the management of sepsis is uncertain. This study investigated the dynamic expression of C5aR and C5L2 on neutrophils and their effects on neutrophil function. We found that sepsis patients displayed low expression levels of C5aR and C5L2 on neutrophils compared to healthy and systemic inflammatory response syndrome (SIRS) subjects, and this expression pattern was correlated with disease severity. Additionally, the expression levels of C5aR and C5L2 were associated with the survival of sepsis patients. In vitro, the addition of C5a significantly reduced C5aR and C5L2 expression levels and IL-8 production in neutrophils from sepsis patients. Those findings suggest that the reduced expression of C5aRs was associated with the functional impairment of neutrophils and a poor prognosis for sepsis patients. Overall, these findings may help establish C5aRs expression levels as early markers to predict the severity of sepsis.

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Acknowledgements

We appreciate all septic individuals, SIRS individuals and healthy participants in this study. The study was approved and has been reviewed by the ethics committee of our 302 Hospital. This work was supported by grants from the National Science Fund for Outstanding Young Scholars (No. 81222024), the National Science Fund for Distinguished Young Scholars (No. 81400626) and the Beijing Natural Science Foundation (No. 714428).

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Author notes

  1. Ruonan Xu, Fang Lin and Chunmei Bao: These authors contributed equally to this study.

  2. Dr FS Wang, Research Center for Biological Therapy, Beijing 302 Hospital, Beijing 100039, China. E-mail: fswang302@163.com

  3. Dr Z Zhang, Research Centre for Biological Therapy, Beijing 302 Hospital, Beijing 100039, China. E-mail: zhangzheng1975@aliyun.com

Authors and Affiliations

  1. Research Centre for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China

    Ruonan Xu, Siyu Wang, Lei Jin, Zheng Zhang & Fu-Sheng Wang

  2. The Institute of Intensive Care Unit, Beijing 302 Hospital, Beijing, China

    Fang Lin, Huihuang Huang, Chengcheng Ji, Lijian Sun & Ke Li

  3. Centre of Clinical Laboratory Medicine, Beijing 302 Hospital, Beijing, China

    Chunmei Bao

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  1. Ruonan Xu
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Xu, R., Lin, F., Bao, C. et al. Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis. Cell Mol Immunol 13, 103–109 (2016). https://doi.org/10.1038/cmi.2014.136

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