title: alpha-Melanocyte-stimulating hormone protects the allograft in experimental heart transplantation.
abstract: BACKGROUND
  With the increasing need for organ transplantation and the use of "marginal" organs, novel approaches are sought to increase the efficiency and survival of transplanted tissue. We tested the idea that treatment with the anti-inflammatory peptide, alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous hormone that does not cause marked immunosuppression but does reduce reperfusion injury, may protect allografts and prolong their survival.
  
  
  METHODS
  Donor cardiac grafts (Brown Norway) were transplanted heterotopically into the abdomen of recipient (Lewis) rats. Treatments consisted of intraperitoneal injections of Nle DPhe -alpha-MSH (NDP-alpha-MSH) or saline from the time of transplantation until sacrifice or spontaneous rejection. Allografts were removed on day 1, day 4, or at the time of rejection and examined for histopathology and expression of molecules prominent in reperfusion injury, transplant rejection, and apoptosis.
  
  
  RESULTS
  NDP-alpha-MSH treatment caused a significant increase in allograft survival and a marked decrease in leukocyte infiltration. Expression of molecules such as endothelin 1, chemokines, and adhesion molecules, which are involved in allograft rejection, was significantly inhibited in NDP-alpha-MSH-treated rats.
  
  
  CONCLUSIONS
  The results indicate that protection of the allograft from early injury with alpha-MSH can postpone rejection. Addition of this early protection with the peptide to usual treatment with immunosuppressive agents may, therefore, improve success of organ transplants.
authors.affiliation: Division of Liver Transplantation, Ospedale Maggiore di Milano IRCCS, Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gatti
authors.forename: Gualtiero
authors.initials: G
authors.lastname: Colombo
authors.forename: Roberto
authors.initials: R
authors.lastname: Buffa
authors.forename: Flavia
authors.initials: F
authors.lastname: Turcatti
authors.forename: Letizia
authors.initials: L
authors.lastname: Garofalo
authors.forename: Nadia
authors.initials: N
authors.lastname: Carboni
authors.forename: Luca
authors.initials: L
authors.lastname: Ferla
authors.forename: Luigi R
authors.initials: LR
authors.lastname: Fassati
authors.forename: James M
authors.initials: JM
authors.lastname: Lipton
authors.forename: Anna
authors.initials: A
authors.lastname: Catania
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D019332:Endothelin-1 / Q000235:genetics; D053222:Fas Ligand Protein; D015870:Gene Expression / Q000187:drug effects; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D016027:Heart Transplantation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D019332:Endothelin-1; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D009566:Nitrates; D009573:Nitrites; D020574:Proto-Oncogene Proteins c-sis; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D000521:alpha-MSH; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat