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

• Published in: Cellular & molecular immunology Vol. 13; no. 1; pp. 103 - 109
• Main Authors: Xu, Ruonan, Lin, Fang, Bao, Chunmei, Huang, Huihuang, Ji, Chengcheng, Wang, Siyu, Jin, Lei, Sun, Lijian, Li, Ke, Zhang, Zheng, Wang, Fu-Sheng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2016; Nature Publishing Group
• Subjects: Adult; Aged; Antibodies; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Complement C5a - immunology; Complement C5a - pharmacology; Complement component C5a; Female; Gene Expression Regulation; Humans; Immunology; Inflammation; Interleukin 8; Interleukin-8 - genetics; Interleukin-8 - immunology; Leukocytes (neutrophilic); Male; Medical Microbiology; Medical prognosis; Microbiology; Middle Aged; Neutrophils; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - pathology; Primary Cell Culture; Prognosis; Receptor, Anaphylatoxin C5a - genetics; Receptor, Anaphylatoxin C5a - immunology; Receptors, Chemokine - genetics; Receptors, Chemokine - immunology; research-article; Sepsis; Sepsis - diagnosis; Sepsis - immunology; Sepsis - mortality; Sepsis - pathology; Severity of Illness Index; Signal Transduction; Survival Analysis; Systemic inflammatory response syndrome; Treatment Outcome; Vaccine; 严重程度; 中性粒细胞; 功能障碍; 受体介导; 细胞功能; 脓毒症; 补体; 预后; complement 5a; complement 5a receptor; neutrophil; prognosis; sepsis
• ISSN: 1672-7681; 2042-0226; 2042-0226
• DOI: 10.1038/cmi.2014.136

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 neutrophits 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.