title: Deazaadenosine prevents leukozyte evasion during acute cardiac allograft rejection by suppression of adhesion molecule expression.
abstract: BACKGROUND
  In the initial phase after cardiac transplantation, mononuclear cells infiltrate the graft initiating a relevant impulse for rejection. 3-Deazaadenosin (c3Ado), an analog of adenosine, has demonstrated in vitro anti-inflammatory properties. Furthermore, in vivo studies on arteriosclerosis development and septic myocardial dysfunction c3Ado revealed reduced cellular infiltration. In addition ischemia and reperfusion injury could be diminished in a pulmonary animal model. The aim of our study was to investigate the properties of c3Ado to reduce adhesion molecule expression and cellular infiltration in a fully allogeneic cardiac transplant model.
  
  
  RESULTS
  Lewis rats were challenged with Wistar-Furth cardiac allografts. Untreated grafts were rejected within 7 days (group 1). In group 2, animals received 2 x 5 mg c3Ado SC per day. Grafts were harvested on days 1, 3, and 6 after transplantation for further examination (n = 4 per group and time point). Immunohistochemical examination revealed significant reduction of graft-infiltrating MHC II positive cells, T-cell receptor positive cells (R73), as well as ED1-positive monocytes and macrophages (P < .01) at days 3 and 6 after transplantation. Adhesion molecule (ICAM-1, VCAM-1) expression on days 1 and 3 after transplantation was almost completely diminished in c3Ado-treated grafts.
  
  
  CONCLUSIONS
  Thus, c3Ado is able to reduce graft infiltration by preventing leukocyte evasion through the suppression of adhesion molecule expression. This may be a novel strategy to protect transplanted organs from early damage after transplantation and extend organ survival after transplantation.
authors.affiliation: Department of Internal Medicine, Division of Cardiology and Angiology, University Giessen, School of Medicine, Giessen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Fingerhuth
authors.forename: H
authors.initials: H
authors.lastname: Hölschermann
authors.forename: H
authors.initials: H
authors.lastname: Grimm
authors.forename: M
authors.initials: M
authors.lastname: Schaub
authors.forename: H
authors.initials: H
authors.lastname: Tillmanns
authors.forename: R C
authors.initials: RC
authors.lastname: Braun-Dullaeus
authors.forename: T H W
authors.initials: TH
authors.lastname: Stadlbauer
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology; D014372:Tubercidin / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000949:Histocompatibility Antigens Class II; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014372:Tubercidin