Anti-coxsackievirus B3 neutralizing antibodies with pathological potential
Autor: | R. Rozek, H. M. Arizpe, R. Crawley, M. W. Cunningham, C. J. Gauntt, A. L. Higdon |
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Rok vydání: | 1991 |
Předmět: |
Male
Myocarditis medicine.drug_class Immunoblotting Cross Reactions Myosins Antibodies Viral Monoclonal antibody Epitope Virus Proinflammatory cytokine Epitopes Mice medicine Animals Macrophage Skin biology business.industry Myocardium Antibodies Monoclonal medicine.disease Enterovirus B Human Cytolysis Immunology biology.protein Female Binding Sites Antibody Antibody Cardiology and Cardiovascular Medicine business |
Zdroj: | European Heart Journal. 12:124-129 |
ISSN: | 1522-9645 0195-668X |
DOI: | 10.1093/eurheartj/12.suppl_d.124 |
Popis: | Adolescent CD-1 mice inoculated with coxsackievirus B3 (CVB3m) will develop acute myocarditis with focal lesions by 7 days post-inoculation (p.i.). Administration of murine sera containing anti-CVB3m-neutralizing antibodies into CVB3m-inoculated mice at 3 days p.i. will exacerbate myocarditis, suggesting the presence of pathological antibodies. To study potential pro-inflammatory properties of virus-induced antibodies, a panel of anti-CVB3m-neutralizing monoclonal antibodies (mAbs) was generated. Several studies demonstrated shared epitopes between CVB3m particles and cultured murine cardiac or neonatal skin fibroblasts: (1) one or more mAbs bound to cultured cardiac fibroblasts; (2) several mAbs can participate in complement-mediated lysis of neonatal skin fibroblasts; and (3) at least one mAbs stimulated synthesis of a macrophage chemoattractant from cultured neonatal skin fibroblasts. Injection of one mAb in three doses, each of about 5 micrograms, into adolescent male CD-1 mice induced focal myocarditic lesions which were similar to CVB3m-induced lesions. One mAb induced a diffuse interstitial hypercellularity in most mice and two mAbs did not induce detectable cardiopathology. These data suggest that some anti-CVB3m neutralizing idiotypes (antibodies) which initially can provide protection via virus clearance mechanisms can also bind to cross-reacting epitopes on normal tissues. Binding of antibodies to normal heart tissues could stimulate proinflammatory reactions by several mechanisms and sustain myocarditis. |
Databáze: | OpenAIRE |
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