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

2004; Elsevier BV; Volume: 10; Issue: 7 Linguagem: Inglês

10.1016/j.bbmt.2004.04.001

1523-6536

Armin Gerbitz, Patricia C. Ewing, Andrea Wilke, Thomas Schubert, Günther Eißner, B. Dietl, Reinhard Andreesen, Kenneth R. Cooke, Ernst Holler,

Neonatal Health and Biochemistry

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.