Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis.
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.
Research Centre for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China.
Ruonan
R
Xu
The Institute of Intensive Care Unit, Beijing 302 Hospital, Beijing, China.
Fang
F
Lin
Centre of Clinical Laboratory Medicine, Beijing 302 Hospital, Beijing, China.
Chunmei
C
Bao
The Institute of Intensive Care Unit, Beijing 302 Hospital, Beijing, China.
Huihuang
H
Huang
The Institute of Intensive Care Unit, Beijing 302 Hospital, Beijing, China.
Chengcheng
C
Ji
Research Centre for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China.
Siyu
S
Wang
Research Centre for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China.
Lei
L
Jin
The Institute of Intensive Care Unit, Beijing 302 Hospital, Beijing, China.
Lijian
L
Sun
The Institute of Intensive Care Unit, Beijing 302 Hospital, Beijing, China.
Ke
K
Li
Research Centre for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China.
Zheng
Z
Zhang
Research Centre for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China.
Fu-Sheng
FS
Wang
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015936:Complement C5a / Q000276:immunology / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D061251:Primary Cell Culture; D011379:Prognosis; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000276:immunology*; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D012720:Severity of Illness Index; D015398:Signal Transduction; D016019:Survival Analysis; D016896:Treatment Outcome
D015415:Biomarkers; C488033:C5AR1 protein, human; C417003:C5aR2 protein, human; D016209:Interleukin-8; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; D015936:Complement C5a