Complement activation in muscle fiber necrosis: Demonstration of the membrane attack complex of complement in necrotic fibers
- 1 September 1982
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 12 (3), 289-296
- https://doi.org/10.1002/ana.410120314
Abstract
The membranolytic C5b-9 complement membrane attack complex (MAC) is assembled after activation of either the classic or the alternative complement pathway. The quaternary configuration of the MAC macromolecule presents neoantigenic determinants not present on precursor molecules. Consequently, antibodies specific for these neoantigen(s) do not detect nonspecifically bound native complement precursors of MAC. By means of antibodies rendered specific for MAC neoantigen(s), MAC was localized by the immunoperoxidase reaction in cryostat sections of human muscle. In 66 biopsy specimens containing necrotic muscle fibers (Duchenne dystrophy, 13; other dystrophies, 15; inflammatory myopathies, 31; miscellaneous myopathies, 7) all of the necrotic fibers reacted for MAC neoantigen(s). C3 and C9 were also consistently localized in necrotic fibers, but localization of C1q, C4, and IgG was variable and often did not exceed background staining. None of the nonnecrotic fibers reacted for immunoglobulin or complement. Detection of MAC neoantigen(s) in necrotic fibers in a wide variety of muscle diseases unambiguously shows that (1) the lytic complement pathway is consistently activated and participates in muscle fiber necrosis in vivo, and (2) complement reaction products are generated that can stimulate cellular infiltration and phagocytosis of the necrotic fiber. The findings also suggest that cell necrosis in general may involve participation of complement.Keywords
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