Induction of heme oxygenase-1 improves the survival of pancreas grafts by prevention of pancreatitis after transplantation.

Abstract

BACKGROUND:

Ischemia/reperfusion (I/R) injury after pancreas transplantation might result in graft pancreatitis. The role of heme oxygenase-1 (HO-1) in pancreas transplantation and prevention of graft pancreatitis is unknown.

METHOD:

We studied the impact of HO-1 induction with cobalt protoporphyrin (CoPP) in experimental pancreas transplantation with moderate (6 hr) and prolonged (20 hr) cold ischemic time (CIT). Donor animals received CoPP 5 mg/kg intraperitoneal at 48 hr or intraperitoneal saline injections in the corresponding control groups before procurement. Harvested grafts were perfused with HTK solution and stored at 4 degrees C.

RESULTS:

After prolonged CIT, graft survival was 100% with CoPP pretreatment in contrast to only 37.5% without pretreatment. CoPP-pretreated grafts demonstrated an unimpaired endocrine graft function at moderate and prolonged CIT. Serum lipase activity as a sign of exocrine preservation was significantly lower. In addition, morphological architecture was well preserved. CoPP pretreatment markedly increased HO-1 gene expression in donor pancreas (130-fold increase) by means of quantitative reverse transcriptase -polymerase chain reaction. Immunohistochemical examinations showed that the increase of HO-1 on the protein level was related to HO-1-positive donor macrophages in the pancreas grafts. HO-1 overexpression was accompanied by significant decrease of proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-2, IL-6, interferon-y, and by significant increase of the anti-inflammatory cytokine IL-10 and less expression of adhesion molecules such as e- and p-selectins.

CONCLUSIONS:

HO-1 is highly inducible in the allograft rat pancreas and associated with a survival benefit and good graft function after transplantation. This study contributes to the beneficial potentials of HO-1 for the prevention of graft pancreatitis.

• Authors: Thomas Becker, Andreas Meyer Zu Vilsendorf, Taivankhuu Terbish, Jürgen Klempnauer, Anne Jörns
• Journal: Transplantation (Transplantation) Vol. 84 Issue 12 Pg. 1644-55 (Dec 27 2007) ISSN: 0041-1337 [Print] United States
• PMID: 18165777 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• DNA Primers
• Metalloporphyrins
• Tumor Necrosis Factor-alpha
• Heme Oxygenase-1

Topics

• Animals
• Blood Glucose (metabolism)
• DNA Primers
• Enzyme Induction
• Graft Survival (physiology)
• Heme Oxygenase-1 (biosynthesis, genetics)
• Humans
• Metalloporphyrins (analysis)
• Pancreas Transplantation (pathology, physiology)
• Pancreatitis (prevention & control)
• Postoperative Complications (prevention & control)
• Rats
• Rats, Inbred Lew
• Reverse Transcriptase Polymerase Chain Reaction
• Transplantation, Homologous (physiology)
• Tumor Necrosis Factor-alpha (metabolism)