title: Expression of intercellular adhesion molecule-1 in murine hearts with acute myocarditis caused by coxsackievirus B3.
abstract: A cell-mediated autoimmune mechanism has been strongly implicated in the pathogenesis of viral myocarditis. Using a murine model of myocarditis caused by coxsackievirus B3 (CVB3), we previously reported that the heart is infiltrated first by natural killer cells, which express a cytolytic factor, perforin, and then by activated T cells. This action may play an important role in the pathogenesis of the observed myocardial cell damage. Cell-cell contact and adhesion is required in immune responses, and intercellular adhesion molecule-1 (ICAM-1), which is a ligand for lymphocyte function-associated antigen-1 (LFA-1), plays an important role in this process. To investigate the essential role of the ICAM-1/LFA-1 pathway in the cell-mediated cytotoxicity involved in viral myocarditis, we examined by immunofluorescence the expression of ICAM-1 in murine hearts with acute myocarditis caused by CVB3. We also evaluated the induction of ICAM-1 in cultured cardiac myocytes treated with cytokines by immunofluorescence and Northern blot hybridization. Furthermore, we analyzed the effects of in vivo administration of anti-ICAM-1 mAbs on the inflammation associated with acute viral myocarditis. We found that CVB3-induced murine acute myocarditis resulted in enhanced expression of ICAM-1 in myocardial cells. The expression of ICAM-1 in myocardial cells could be induced in vitro by IFN-gamma and TNF-alpha, which were shown to be synthesized by the infiltrating cells. In vivo treatment with F(ab')2 fragments of an anti-ICAM-1 mAb significantly reduced the myocardial inflammation induced by CVB3. These data strongly suggest that the expression of ICAM-1 in myocardial cells plays a critical role in the cell-mediated cytotoxicity involved in acute viral myocarditis.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Seko
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
mesh_terms: D000208:Acute Disease; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured / Q000737:chemistry; D003384:Coxsackievirus Infections; D005260:Female; D005455:Fluorescent Antibody Technique; D006352:Heart Ventricles / Q000166:cytology; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009130:Muscle, Smooth / Q000166:cytology; D009205:Myocarditis / Q000382:microbiology*; D009206:Myocardium / Q000737:chemistry* / Q000166:cytology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011991:Receptors, Virus / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma