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

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...

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Bibliographic Details
Published in:Biology of blood and marrow transplantation 2004-07, Vol.10 (7), p.461-472
Main Authors: Gerbitz, Armin, Ewing, Patricia, Wilke, Andrea, Schubert, Thomas, Eissner, Günther, Dietl, Barbara, Andreesen, Reinhard, Cooke, Kenneth R, Holler, Ernst
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - immunology
BMT
Bone Marrow Transplantation - immunology
Cobalt - administration & dosage
CoPP
Cytokines
Cytokines - blood
Enzyme Induction - drug effects
Enzyme Induction - immunology
Graft vs Host Disease - blood
Graft vs Host Disease - etiology
Graft vs Host Disease - mortality
GVHD
Heme oxygenase
Heme Oxygenase (Decyclizing) - biosynthesis
Heme Oxygenase (Decyclizing) - immunology
Heme Oxygenase-1
Intestinal Mucosa - immunology
Intestinal Mucosa - pathology
Liver - immunology
Liver - pathology
LPS
Lymphocyte Activation - immunology
Membrane Proteins
Mice
Protoporphyrin
Protoporphyrins - administration & dosage
Spleen - immunology
Spleen - pathology
Transplantation Conditioning - methods
Transplantation, Homologous
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Summary: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.
ISSN:1083-8791
1523-6536
DOI:10.1016/j.bbmt.2004.04.001