HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsumoto, Y. Articles by Kohyama, K. Search for Related Content PubMed PubMed Citation Articles by Matsumoto, Y. Articles by Kohyama, K.

C Protein-Induced Myocarditis and Subsequent Dilated Cardiomyopathy: Rescue from Death and Prevention of Dilated Cardiomyopathy by Chemokine Receptor DNA Therapy¹

Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan

Severe experimental autoimmune myocarditis and subsequent dilated cardiomyopathy (DCM) were successfully produced in Lewis rats by immunization with recombinant cardiac C protein. Seventy-five percent of immunized rats died between days 15 and 49 postimmunization, and all of the survived rats showed typical DCM characterized by the presence of ventricular dilatation and extensive fibrosis. Immunopathological and chemokine analysis during the acute phase revealed that there were marked macrophage infiltration with myocyte necrosis and up-regulation of MCP-1 and IFN--inducible protein-10 (IP-10). Based on these findings, we prepared plasmid DNAs encoding the binding site of CCR2 and CXCR3, which are receptors for MCP-1 and IP-10, respectively. The culture supernatant of cells transfected with these DNAs inhibited the migration of T cells and macrophages induced by MCP-1 and IP-10. Remarkably, administration of the DNAs to C protein-immunized rats prevented the disease progression and rescued animals from death. The present study has demonstrated for the first time that gene therapy targeting the chemokine receptor could be a powerful tool for the control of experimental autoimmune myocarditis and DCM.

This article has been cited by other articles:

				Y. Katsumata, M. Harigai, T. Sugiura, M. Kawamoto, Y. Kawaguchi, Y. Matsumoto, K. Kohyama, M. Soejima, N. Kamatani, and M. Hara Attenuation of Experimental Autoimmune Myositis by Blocking ICOS-ICOS Ligand Interaction J. Immunol., September 15, 2007; 179(6): 3772 - 3779. [Abstract] [Full Text] [PDF]

				Y. Matsumoto, I.-K. Park, and K. Kohyama B-Cell Epitope Spreading Is a Critical Step for the Switch from C-Protein-Induced Myocarditis to Dilated Cardiomyopathy Am. J. Pathol., January 1, 2007; 170(1): 43 - 51. [Abstract] [Full Text] [PDF]

				V. R. Taqueti, N. Grabie, R. Colvin, H. Pang, P. Jarolim, A. D. Luster, L. H. Glimcher, and A. H. Lichtman T-bet Controls Pathogenicity of CTLs in the Heart by Separable Effects on Migration and Effector Activity J. Immunol., November 1, 2006; 177(9): 5890 - 5901. [Abstract] [Full Text] [PDF]