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Increased susceptibility to complement attack due to down-regulation of decay-accelerating factor/CD55 in dysferlin-deficient muscular dystrophy

Item Type:Article
Title:Increased susceptibility to complement attack due to down-regulation of decay-accelerating factor/CD55 in dysferlin-deficient muscular dystrophy
Creators Name:Wenzel, K. and Zabojszcza, J. and Carl, M. and Taubert, S. and Lass, A. and Harris, C.L. and Ho, M. and Schulz, H. and Hummel, O. and Huebner, N. and Osterziel, K.J. and Spuler, S.
Abstract:Dysferlin is expressed in skeletal and cardiac muscles. However, dysferiin deficiency results in skeletal muscle weakness, but spares the heart. We compared intraindividual mRNA expression profiles of cardiac and skeletal muscle in dysferlin-deficient SJL/J mice and found down-regulation of the complement inhibitor, decay-accelerating factor/CD55, in skeletal muscle only. This finding was confirmed on mRNA and protein levels in two additional dysferlin-deficient mouse strains, A/J mice and Dysf-/- mice, as well as in patients with dysferlin-deficient muscular dystrophy. In vitro, the absence of CD55 led to an increased susceptibility of human myotubes to complement attack. Evidence is provided that decay-accelerating factor/CD55 is regulated via the myostatin-SMAD pathway. In conclusion, a novel mechanism of muscle fiber injury in dysferlin-deficient muscular dystrophy is demonstrated, possibly opening therapeutic avenues in this to date untreatable disorder.
Keywords:CD55 Antigens, Complement System Proteins, Down-Regulation, Inbred C57BL Mice, Membrane Proteins, Muscular Dystrophies, Myostatin, Skeletal Muscle , Skeletal Muscle Fibers, Smad3 Protein, Transforming Growth Factor beta, Animals, Mice
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:175
Number:9
Page Range:6219-6225
Date:1 November 2005
Official Publication:http://www.jimmunol.org/cgi/content/abstract/175/9/6219
PubMed:View item in PubMed

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