title: Attenuation of acute rat renal allograft rejection by apolipoprotein E-mimetic Peptide.
abstract: BACKGROUND
  In addition to its well-described role in lipid metabolism, apolipoprotein E (ApoE) exerts immunomodulatory functions. A protective role of ApoE and ApoE-mimetic peptide (ApoE(133-149)) application was documented in several inflammatory disorders. In this study, we test the hypothesis that ApoE(133-149) promotes renal allograft survival.
  
  
  METHODS
  Dark Agouti, Brown Norway, and Fischer 344 kidneys were transplanted to Lewis rats to investigate fatal and reversible acute rejection. Apolipoprotein E expression was assessed in intravascular leukocytes of renal grafts, in graft tissue and in recipient blood plasma. Recipients of Brown Norway kidneys were treated with ApoE(133-149), and graft survival was monitored until day 100. Graft infiltration, cytokine, and chemokine production were analyzed.
  
  
  RESULTS
  Intravascular graft leukocytes and renal tissue obtained from animals undergoing reversible acute rejection expressed increased levels of ApoE mRNA, whereas during fatal rejection, ApoE expression was reduced or remained unchanged. Animals treated with ApoE(133-149) showed prolonged allograft survival, which was associated with a reduced infiltration of CD8 and α/β T-cell receptor-expressing cells, diminished Granzyme B mRNA expression, and decreased caspase-3 activation.
  
  
  CONCLUSIONS
  Endogenous ApoE overexpression and exogenous application of ApoE(133-149) seem to protect renal allografts from fatal acute rejection. This effect was associated with a reduced influx of cytotoxic T cells.
authors.affiliation: 1 Department of General and Thoracic Surgery, Laboratory of Experimental Surgery, Justus-Liebig-University Giessen, Giessen, Germany. 2 Department of Biochemistry, Justus-Liebig-University Giessen, Giessen, Germany. 3 Department of Internal Medicine II, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Zakrzewicz
authors.forename: Khusin
authors.initials: K
authors.lastname: Kutlimuratov
authors.forename: Srebrena
authors.initials: S
authors.lastname: Atanasova
authors.forename: Dariusz
authors.initials: D
authors.lastname: Zakrzewicz
authors.forename: Martin
authors.initials: M
authors.lastname: Reichert
authors.forename: Jessica
authors.initials: J
authors.lastname: Schmitz
authors.forename: Jochen
authors.initials: J
authors.lastname: Wilhelm
authors.forename: Günter
authors.initials: G
authors.lastname: Lochnit
authors.forename: Winfried
authors.initials: W
authors.lastname: Padberg
authors.forename: Veronika
authors.initials: V
authors.lastname: Grau
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000627:therapeutic use*; D002465:Cell Movement; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D006084:Graft Rejection / Q000517:prevention & control*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D059467:Transcriptome
chemical_list: D001057:Apolipoproteins E; D018925:Chemokines; D016207:Cytokines; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta