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

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

162 Zitate (Scopus)


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.

Seiten (von - bis)765-767
FachzeitschriftFASEB Journal
PublikationsstatusVeröffentlicht - Apr. 2004
Extern publiziertJa


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