Regulation by C5a of Neutrophil Activation

during Sepsis

Immunity, 19, 193-202, 2003

Speaker: 劉倩如                                 Time: 11/12/2003 13:00~14:00

Commentator: 謝奇璋醫師                         Place: 601教室

Sepsis is often associated with a high mortality rate despite the treatment with antibiotics. It is well documented that complement activation, production of cytokines and unregulated inflammatory responses may occur in patients with spesis.¹ In the early stage of sepsis, the complement activation product C5a has been shown to play an important inflammatory role in rats following cecal ligation and puncture (CLP) or subsequent to infusion of LPS. In this study, the authors attempted to define the role of C5a in neutrophils activation during sepsis. In vitro exposure of neutrophils to C5a causes increased levels of IkBα, decreased NF-kB-dependent gene transcription of TNFα, thus decreased lipopolysaccharide (LPS)-induced TNFα production. The neutrophils from CLP induced septic rats revealed the same phenomenon. Besides, by using of a C5a blockade couldreverse TNFα production by neutrophils. In contrast, C5a has a diverse effect on alveolar macrophage because C5a failed to suppress LPS-induced production of TNFα through IkBα. These data suggest a previously unrecognized cell-specific inhibitory role of C5a for innate immune responses of neutrophils during sepsis through the increased level of IkBa. Their results therefore resolve the underlying mechanism of sepsis and may be helpful for the development of new therapeutic target.

References

1.      Czermak, B.J., et al. Protective effects of C5a blockade in sepsis. Nat Med. 1999 Jul;5(7):788-92.

2.      Riedemann, N.C., et al. Increased C5a receptor expression in sepsis. J Clin Invest.  2002 Jul;110(1):101-8.