Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts.

Kenichiro Yamashita, James McDaid, Robert Ollinger, Tung Yu Tsui, Pascal O. Berberat, Anny Usheva, Eva Csizmadia, R. Neal Smith, Miguel P. Soares, Fritz H. Bach

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

Biliverdin, a product of heme oxygenase-1 (HO-1) enzymatic action, is converted into bilirubin, which has been considered a waste product in the past. We now show that administration of biliverdin has a salutary effect in organ transplantation. A brief course of treatment with biliverdin leads to long-term survival of H-2 incompatible heart allografts. Furthermore, those recipients harboring long-surviving (>100 days) allografts were tolerant to donor antigens indicated by the acceptance of second donor strain hearts but not third-party grafts. Treatment with biliverdin decreased intragraft leukocyte infiltration and inhibited T cell proliferation. Likely related to tolerance induction, biliverdin interferes with T cell signaling by inhibiting activation of nuclear factor of activated T cells (NFAT) and nuclear factor kappaB (NF-kappaB), two transcription factors involved in interleukin-2 (IL-2) transcription and T cell proliferation, as well as suppressing Th1 interferon-gamma (IFN-gamma) production in vitro. These findings support the potential use of biliverdin, a natural product, in transplantation and other T cell mediated immune disorders.

Original languageEnglish
Pages (from-to)765-767
Number of pages3
JournalFASEB Journal
Volume18
Issue number6
DOIs
StatePublished - Apr 2004
Externally publishedYes

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