title: Heme oxygenase-1 in organ transplantation.
abstract: Cells have a plethora of defense mechanisms that are activated upon exposure to oxidative stress. These aim at limiting the deleterious effects of oxidative stress and re-establishing homeostasis. In the particular context of organ transplantation, these defense mechanisms contribute to sustain graft survival via at least two interrelated mechanisms. First, cytoprotection per se should support survival and function of cells within a transplanted organ. Second, cytoprotection could reduce immunogenicity of the graft and modulate the activation of the recipient's immune system to promote regulatory (suppressive) responses that sustain graft survival. Others and we have gathered evidence, to suggest that the stress-responsive enzyme Heme Oxygenase-1 (HO-1 encoded by the gene Hmox1) acts in such a manner. Upon organ transplantation, HO-1 is ubiquitously expressed in a transplanted organ, becoming the rate-limiting enzyme in the catabolism of heme into carbon monoxide (CO), iron (Fe) and biliverdin (1). There is accumulating evidence to support the notion that HO-1 expression in a graft and in the recipient can prevent rejection and promote immune tolerance. We will argue that these effects are mediated to a large extent by limiting the deleterious effects of free heme as well as by the inherent cytoprotective and/or anti-inflammatory effects of the end-products generated via heme catabolism.
authors.affiliation: Instituto Gulbenkian de Ciencia, Oeiras, Portugal, Oeiras, Portugal. mpsoares@igc.gulbenkian.pt
authors.forename: Miguel P
authors.initials: MP
authors.lastname: Soares
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Bach
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000201:enzymology* / Q000517:prevention & control; D051547:Heme Oxygenase-1 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D016377:Organ Transplantation; D015427:Reperfusion Injury / Q000517:prevention & control
chemical_list: D051547:Heme Oxygenase-1