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 language | English (US) |
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Pages (from-to) | 461-472 |
Number of pages | 12 |
Journal | Biology of Blood and Marrow Transplantation |
Volume | 10 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2004 |
Externally published | Yes |
Keywords
- BMT
- CoPP
- Cytokines
- GVHD
- Heme oxygenase
- LPS
- Protoporphyrin
ASJC Scopus subject areas
- Hematology
- Transplantation