C5a causes limited, polymorphonuclear cell-independent, mesenteric ischemia/reperfusion-induced injury.
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.
D000818:Animals; D015703:Antigens, CD; D003182:Complement C5 / Q000172:deficiency / Q000235:genetics; D015936:Complement C5a; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D015777:Eicosanoids / Q000096:biosynthesis; D039441:Integrin alpha4 / Q000032:analysis; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D017538:Mesenteric Artery, Superior; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018375:Neutrophil Activation / Q000276:immunology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology*; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism
D015703:Antigens, CD; D003182:Complement C5; D015938:Complement Membrane Attack Complex; D015777:Eicosanoids; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4; D015936:Complement C5a