Induction of heme oxygenase-1 before conditioning results in improved survival and reduced graft-versus-host disease after experimental allogeneic bone marrow transplantation

Armin Gerbitz, Patricia Ewing, Andrea Wilke, Thomas Schubert, Günther Eissner, Barbara Dietl, Reinhard Andreesen, Kenneth R. Cooke, Ernst Holler

Research output: Contribution to journalArticlepeer-review

Abstract

Acute graft-versus-host disease (aGVHD) remains one of the main obstacles after allogeneic bone marrow transplantation (BMT). Using a well-established mouse BMT model in which aGVHD is induced across a haploidentical mismatch, we show that the expression of heme oxygenase-1 (HO-1) can be induced by cobalt-protoporphyrin IX (CoPP) in aGVHD target organs such as liver and bowel and that the induction of HO-1 before BMT results in improved overall survival and reduced aGVHD. Serum levels of proinflammatory cytokines were markedly reduced in CoPP-treated animals. Recipients displayed less damage to the intestinal mucosa, and this resulted in reduced serum lipopolysaccharide levels at day 6 after transplantation. Peritoneal cells and CD45+ liver cells isolated from mice that received transplants strongly expressed HO-1 and displayed a reduction in the expression of activation markers such as CD11b, CD80, and major histocompatibility complex class I. This resulted in reduced T-cell activation ex vivo. These results demonstrate that the induction of HO-1 before high-dose conditioning protects the host in multiple ways and effectively ameliorates aGVHD.

Original languageEnglish (US)
Pages (from-to)461-472
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume10
Issue number7
DOIs
StatePublished - Jul 2004
Externally publishedYes

Keywords

  • BMT
  • CoPP
  • Cytokines
  • GVHD
  • Heme oxygenase
  • LPS
  • Protoporphyrin

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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