Abstract
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
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Comparative Study
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD
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Complement C5 / deficiency
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Complement C5 / genetics
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Complement C5a*
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Complement Membrane Attack Complex / physiology*
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Eicosanoids / biosynthesis
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Integrin alpha4 / analysis
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Intestinal Mucosa / blood supply*
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / pathology
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Lung / metabolism
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Lung / pathology
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Male
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Mesenteric Artery, Superior*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neutrophil Activation / immunology
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Receptor, Anaphylatoxin C5a
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Receptors, Complement / antagonists & inhibitors
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Recombinant Proteins
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Reperfusion Injury / etiology
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Reperfusion Injury / pathology*
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Time Factors
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Vascular Cell Adhesion Molecule-1 / analysis
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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Antigens, CD
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Complement C5
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Complement Membrane Attack Complex
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Eicosanoids
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Receptor, Anaphylatoxin C5a
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Receptors, Complement
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Recombinant Proteins
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Vascular Cell Adhesion Molecule-1
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Integrin alpha4
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Complement C5a