Janus face of complement-driven neutrophil activation during sepsis

• Published in: Seminars in immunology Vol. 37; pp. 12 - 20
• Main Authors: Halbgebauer, R., Schmidt, C.Q., Karsten, C.M., Ignatius, A., Huber-Lang, M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2018
• Subjects: Complement; Infection; Multiple organ failure; Neutrophils; Organ dysfunction; Sepsis; Efb; NADPH; NO; PI-3K; CLP; IgG; SDF-1; CXCR4; Complement; TNF; LPS; NF-κB; S1P; TLR; DAMPs/PAMPs; fH; IL; Neutrophils; Multiple organ failure; Organ dysfunction; MAC; Infection; SOFA; NETs; TCC; ROS; Sepsis; C3aR; C5aR1/2; ERK
• ISSN: 1044-5323; 1096-3618
• DOI: 10.1016/j.smim.2018.02.004

•Two-sided neutrophil response during sepsis can be central for detrimental outcome.•Suppressed response after complement stimulus increases risk of spreading infection.•Excessive neutrophil activity may induce thrombosis and damage of healthy tissues.•Targeted modulation of complement-neutrophil interaction might improve survival. During local and systemic inflammation, the complement system and neutrophil granulocytes are activated not only by pathogens, but also by released endogenous danger signals. It is recognized increasingly that complement-mediated neutrophil activation plays an ambivalent role in sepsis pathophysiology. According to the current definition, the onset of organ dysfunction is a hallmark of sepsis. The preceding organ damage can be caused by excessive complement activation and neutrophil actions against the host, resulting in bystander injury of healthy tissue. However, in contrast, persistent and overwhelming inflammation also leads to a reduction in neutrophil responsiveness as well as complement components and thus may render patients at enhanced risk of spreading infection. This review provides an overview on the molecular and cellular processes that link complement with the two-faced functional alterations of neutrophils in sepsis. Finally, we describe novel tools to modulate this interplay beneficially in order to improve outcome.