Complement in ischemia reperfusion injury.

In the current issue of The American Journal of Pathology Stahl et al describe an important role for the alternative complement pathway in ischemia reperfusion (I/R) of the intestine, using factor D-deficient mice. The requirement for the complement system in I/R-induced tissue injury has been established, but the contribution of the various complement pathways (classical, alternative, and lectin), is largely unknown because, until recently, the tools for such an investigation were not available. The complement split product, C5a, and the terminal membrane attack complex, C5b-9 (MAC), are believed to be responsible for complement-mediated I/R-induced tissue injury, and, therefore, may be targets for therapeutic interventions in clinical settings. More precise understanding of the relevant complement pathway(s) involved in the final generation of C5a and MAC will define the options for therapeutic intervention.