Journal of Leukocyte Biology
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Published online before print August 1, 2003
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0403137

Received for publication April 4, 2003.

Accepted for publication May 21, 2003.

Article

Conceptual perspectives: a key role of C5a/C5aR activation for the development of sepsis

Niels C. Riedemann , Ren-Feng Guo , and Peter A. Ward @

Department of Pathology, University of Michigan Medical School, Ann Arbor

@ To whom correspondence should be addressed. E-mail: pward{at}umich.edu.


  Abstract

In recent studies, evidence has been provided for complement activation early during the onset of experimental sepsis. Excessive production of the anaphylatoxin C5a thereby appears to elicit various harmful effects. Blockade of C5a or C5a receptor (C5aR) at the start of experimental sepsis has been demonstrated to greatly improve survival in rodents. There is evidence that C5a, during the onset of sepsis, enhances the production of various proinflammatory mediators in different cell types. Besides its known, other proinflammatory effects, recent work suggested an inhibitory role of C5a for innate-immune functions of phagocytic cells (phagocytosis, reactive oxygen species production, chemotaxis) during experimental sepsis. This review article provides an overview of the important role of C5a/C5aR activation for the onset and development of sepsis.

Key Words: inflammation • complement • cytokines • LPS • innate immunity • antibody




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