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Role of the complement in experimental sepsis.

¹University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109-0602, USA. pward@umich.edu

Journal of Leukocyte Biology

|September 19, 2007

Summary

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Complement activation products and receptors play a key role in sepsis. Blocking C5a or C5a receptors improves survival in experimental sepsis and may be effective in human septic shock.

Area of Science:

Immunology
Sepsis Pathophysiology

Background:

Complement activation products and receptors are implicated in sepsis.
Experimental sepsis models show complement system involvement.

Purpose of the Study:

To investigate the role of complement activation products and receptors in experimental and human sepsis.
To assess the therapeutic potential of targeting C5a or C5a receptors in sepsis.

Main Methods:

Utilized cecal ligation and puncture (CLP) model in rodents.
Analyzed complement activation products (C3a, C5a) and C5a receptor (C5aR) expression in plasma and tissues.
Evaluated the effect of C5a or C5aR blockade on survival and immune function.

Main Results:

CLP induces complement consumption and C5a generation in rodents.

Related Experiment Videos

Sepsis up-regulates C5a receptors on neutrophils and in organs, with decreased expression correlating with mortality.

Interception of C5a or C5aR improves survival, preserves neutrophil function, and reduces coagulopathy in CLP.

Conclusions:

Complement activation and C5a/C5aR pathways are critical in sepsis pathophysiology.
Targeting C5a or C5aR demonstrates therapeutic efficacy in experimental sepsis.
Findings suggest potential clinical utility of C5a/C5aR blockade in human septic shock.