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The Differing Roles of the Classical and Mannose-Binding Lectin Complement Pathways in the Events following Skeletal Muscle Ischemia-Reperfusion¹

Department of Surgery and Pediatrics, Brigham and Women’s Hospital, and Department of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115

Complement is an important mediator of the injuries observed after skeletal muscle ischemia and subsequent reperfusion. Although the classical pathway had been assumed to be the major pathway of activation leading to injury, the mannose-binding lectin (MBL) pathway might also play a contributing role. In this study, we found that MBL-deficient mice had significant protection after skeletal muscle reperfusion injury compared with wild-type, classical pathway-specific C1q-deficient mice, or MBL-deficient mice reconstituted with recombinant human MBL. MBL-deficient mice, however, were not protected from permeability edema or secondary lung injury after ischemia-reperfusion. These data indicate that blockade of the classical pathway alone (C1q) is protective against permeability edema and remote pulmonary injury but not protective against histologic muscle injury. In contrast, blocking the MBL pathway alone protects against histological injury but is not protective against permeability edema or lung injury. Thus, the activation of both pathways is likely responsible for the full spectrum of injuries observed after skeletal muscle reperfusion injury.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by U.S. Public Health Service Grant P50 GM52585. This work contains data that were presented at the Surgical Forum in the 2004 Annual Congress of the American College of Surgeons.

² Address correspondence and reprint requests to Dr. William G. Austen, Jr., Department of Plastic Surgery, Massachusetts General Hospital, 10 Fruit Street, Boston, MA 02115. E-mail address: wausten{at}partners.org

³ Abbreviations used in this paper: MBL, mannose-binding lectin; rhMBL, recombinant human MBL; HLIR, hind limb ischemia-reperfusion; MASP, MBL-associated serine protease.

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