title: Mechanism of inflammation in murine eosinophilic myocarditis produced by adoptive transfer with ovalbumin challenge.
abstract: BACKGROUND
  Interleukin (IL)-5, RANTES and CC chemokine receptor 3 (CCR3) are essential for induction of eosinophil recruitment in organs, but the precise pathogenesis of eosinophilic myocarditis is still unclear. We investigated the relationships between these cytokines and receptors in the development of inflammation in murine myocarditis produced by adoptive transfer, with reference to eosinophil infiltration and signal transduction.
  
  
  METHODS
  The splenocytes from male donor DBA/2 mice were separated after ovalbumin (OVA) sensitization. These cells had a CD4/CD8 ratio of approximately 3.0. Cells (2.0 x 10(7)) were individually transfused to recipient adoptive male DBA/2 mice, and OVA challenge was performed serially. The heart and spleen of the recipient were analyzed to determine the kinetics of IL-5, RANTES, CCR3 and eosinophil production with simultaneous determination of Janus kinase 3 (JAK3) mRNA.
  
  
  RESULTS
  Approximately 85% of recipient mice developed myocarditis; 35% had recognizable cell infiltration in the left ventricular endocardium, an effect which was absent in control mice. Eosinophilic myocarditis was usually associated with animals having several degenerative changes in myocardial cells, and IL-5, RANTES and CCR3 expressions were usually present in these eosinophils (p < 0.05). CCR3 and JAK3 mRNAs were detected in the spleens and hearts of recipient animals providing histological evidence for kinetics related to eosinophil infiltration.
  
  
  CONCLUSIONS
  The murine model of adoptive transferred myocarditis is suitable for studying the mechanism of eosinophilic myocarditis. A unique pathogenesis of this disorder may be controlled by the synergism of CD4 dominancy in the donor and JAK-STAT signaling in the recipient, which may cause recruitment of eosinophils into heart lesions.
authors.affiliation: Department of Anatomy and Biology, Osaka Medical College, Osaka, Japan. in3017@poh.osaka-med.ac.jp
authors.forename: Masao
authors.initials: M
authors.lastname: Hirasawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ito
authors.forename: Masa-Aki
authors.initials: MA
authors.lastname: Shibata
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Otsuki
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018946:Chemokine CCL5 / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D053616:Janus Kinase 3 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin; D012333:RNA, Messenger / Q000276:immunology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: C515351:Ccr3 protein, mouse; D018946:Chemokine CCL5; D015848:Interleukin-5; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D010047:Ovalbumin; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3