IgM binding to injured tissue precedes complement activation during skeletal muscle ischemia-reperfusion

• Published in: The Journal of surgical research 2004-11, Vol.122 (1), p.29-35
• Main Authors: Chan, Rodney K., Ding, Grace, Verna, Nicola, Ibrahim, Shahrul, Oakes, Sean, Austen Jr, William G., Hechtman, Herbert B., Moore, Francis D.
• Format: Article
• Language: English
• Subjects: Animals; antibody; Biological and medical sciences; complement; Complement Activation; Complement C3 - metabolism; General aspects; Hindlimb; Immunoglobulin M - metabolism; Immunohistochemistry - methods; ischemia/reperfusion; Male; Medical sciences; Mice; Mice, Inbred C57BL; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Reperfusion Injury - blood; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; skeletal muscle; Staining and Labeling; Time Factors; timecourse
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2004.07.005

Skeletal muscle reperfusion injury is mediated by IgM natural antibodies and by complement activation, as shown by the attenuation of reperfusion injury seen in mice with no natural IgM [ 1] and in mice deficient in complement C3 and C4 [ 2]. We postulate that tissue, when ischemic, expresses neoantigens to which preformed natural IgM antibodies bind, in turn producing harmful complement activation and reperfusion injury. C57Bl/6 mice were subjected to 2 h of tourniquet-induced hind limb ischemia followed by variable periods of reperfusion. Two hours of ischemia and 3 h of reperfusion produced severe muscle necrosis and edema. Deposition of IgM and C3 in tissue was assessed using immunohistochemistry on both frozen and Formalin-fixed tissue samples. IgM binding to the endothelium and muscle bundles of the hind limb began during the ischemic period and continued throughout reperfusion up to 6 h. C3 deposition was not present during ischemia and, in contrast, began to appear at 1 h of reperfusion and increased progressively thereafter. These data demonstrate that IgM binding to ischemic tissues precedes the damaging complement activation by a significant period of time. This has important therapeutic implications when considering anti-inflammatory therapy for reperfusion injury.