C5a causes limited, polymorphonuclear cell-independent, mesenteric ischemia/reperfusion-induced injury

Clin Immunol. 2003 Sep;108(3):263-73. doi: 10.1016/s1521-6616(03)00160-8.


C5 is critical in the development of local mucosal damage and inflammation as well as in the development of remote organ injury after mesenteric ischemia/reperfusion (IR). To define the role of C5a in tissue injury, we treated wild-type mice with a cyclic hexapeptide C5a receptor antagonist (C5aRa) and administered recombinant C5a to C5 deficient (C5(-/-)) mice subjected to mesenteric IR. We demonstrate that at 2-h postreperfusion, C5a administered to C5-/- mice during IR induces limited intestinal mucosal injury but failed to cause remote lung injury despite the fact that it upregulated adhesion molecule expression. C5aRa treatment of C5+/+ mice undergoing IR limited local injury and prevented distant organ injury. We conclude that although C5a can trigger certain components of the IR induced injury, other mediators such as C5b-9 and local factors are needed for the complete expression of IR tissue damage.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD
  • Complement C5 / deficiency
  • Complement C5 / genetics
  • Complement C5a*
  • Complement Membrane Attack Complex / physiology*
  • Eicosanoids / biosynthesis
  • Integrin alpha4 / analysis
  • Intestinal Mucosa / blood supply*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mesenteric Artery, Superior*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Activation / immunology
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement / antagonists & inhibitors
  • Recombinant Proteins
  • Reperfusion Injury / etiology
  • Reperfusion Injury / pathology*
  • Time Factors
  • Vascular Cell Adhesion Molecule-1 / analysis
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Antigens, CD
  • Complement C5
  • Complement Membrane Attack Complex
  • Eicosanoids
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • Recombinant Proteins
  • Vascular Cell Adhesion Molecule-1
  • Integrin alpha4
  • Complement C5a