title: Allochimeric molecules and mechanisms in abrogation of cardiac allograft rejection.
abstract: BACKGROUND
  Dendritic cells are professional antigen presenting cells that perform antigen processing and antigen presentation functions and rely on the proper functioning and distribution of the endoplasmic reticulum (ER) and Golgi apparatus and of vesicular trafficking pathways. We previously developed a model system to study the mechanisms governing inhibition of chronic rejection of heart allografts.
  
  
  METHODS
  Heterotopic cardiac transplants were placed intra-abdominally and the major histocompatibility class (MHC) class I allochimeric molecule, [α1h1/u]-RT1.Aa, which contains donor-type (Wistar Furth, WF; RT1u) immunogenic epitopes displayed on recipient-type (ACI, RT1a) sequences, was delivered by portal vein to the recipients of heterotopic hearts. Dendritic cells were isolated from the recipient bone marrow at 1 and 3 days after transplantation and were immunostained or processed for Western blotting with anti-RhoB, translationally controlled tumor protein (TCTP), Sprouty-related (Spred1) protein, ER, and Golgi antibodies.
  
  
  RESULTS
  Western blotting analyses showed the downregulation of RhoB GTPase, TCTP, and Spred1 in dendritic cells isolated from allochimeric molecule-treated rats. Immunostaining showed that in these cells, Spred 1 was shifted to the base of cellular processes, Rho B formed nonvesicular band in the cell equator, and TCTP was highly enriched in the cell nucleus. The Golgi apparatus was drastically reduced in size and formed a tiny nonvesicular aggregate, and the ER partially lost vesicular appearance.
  
  
  CONCLUSIONS
  The function of allochimeric molecule in the abrogation of heart allograft rejection may rely on the downregulation of RhoB pathway components that regulate the structure and function of the ER/Golgi/vesicular trafficking pathways involved in antigen processing and presentation by dendritic cells.
authors.affiliation: Department of Surgery, The Methodist Hospital and The Methodist Hospital Research Institute, Houston, Texas, USA.
authors.forename: T Spencer
authors.initials: TS
authors.lastname: Skelton
authors.forename: Neelam
authors.initials: N
authors.lastname: Tejpal
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Gong
authors.forename: Jacek Z
authors.initials: JZ
authors.lastname: Kubiak
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kloc
authors.forename: Rafik M
authors.initials: RM
authors.lastname: Ghobrial
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism*; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance; D007073:Immunoglobulin E; D020935:MAP Kinase Signaling System; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF; D012097:Repressor Proteins / Q000276:immunology* / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D006649:Histocompatibility Antigens; D012097:Repressor Proteins; C499021:Spred1 protein, rat; C000715649:Tpt1 protein, rat; D000090324:Tumor Protein, Translationally-Controlled 1; C038353:histocompatibility antigens RT, rat; D007073:Immunoglobulin E