Induction of Carbon Monoxide in Donor Animals Prior to Organ Procurement Reduces Graft Immunogenicity and Inhibits Chronic Allograft Dysfunction

Martins, Paulo Ney Aguiar; Reutzel‐Selke, Anja; Jurisch, Anke; Denecke, Christian; Attrot, Kirstin; Pascher, Andreas; Kotsch, Katja; Pratschke, Johann; Neuhaus, P.; Volk, Hans‐Dieter; Tullius, Stefan G.

doi:10.1097/01.tp.0000232716.91887.c5

Cited by 36 publications

(26 citation statements)

References 47 publications

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“…Treatment of donor animals with CoPP to induce HO-1, 24 hours before organ harvesting, reduced the frequency of donor-derived dendritic cells in the graft, which was associated with reduced frequencies of CD4 + cells, CD8 + cells, and alloreactivity [33]. Interestingly, similar effects were reported with the use of a CO donor, methylene chloride, given to the organ donor [34]. Previous studies reported that CO, delivered as a gas to recipient animals, in syngeneic rat kidney transplantation is protective and the combination of CO with biliverdin had additive protective effects [20].…”

Section: Kidney Transplantation and Ho-1supporting

confidence: 66%

Heme oxygenase and renal disease

Jarmi¹,

Agarwal

2009

Current Science Inc

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The cellular content of heme, derived from the breakdown of heme proteins, is regulated via the heme oxygenase (HO) enzyme system. HO catalyzes the rate-limiting step in heme degradation resulting in the formation of iron, carbon monoxide, and biliverdin. Recent studies have focused on the biologic effects of product(s) of this reaction, which have important antioxidant, antiapoptotic, anti-inflammatory, and cytoprotective properties. Two isoforms of the HO enzyme have been described: an inducible isoform (HO-1) and a constitutively expressed isoform (HO-2). Induction of HO-1 occurs as a beneficial response to several injurious stimuli and has been implicated in many clinically relevant disease states including sepsis, hypertension, atherosclerosis, and acute lung and kidney injury. This review focuses on the role of HO-1 in kidney diseases.

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Section: Kidney Transplantation and Ho-1supporting

confidence: 66%

Heme oxygenase and renal disease

Jarmi¹,

Agarwal

2009

Current Science Inc

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“…In addition to its antiinflammatory and anti-apoptotic effects, CO reduced graft immunogenicity and inhibited chronic allograft nephropathy in a rat kidney transplantation model. 22 Although CO may cause serious adverse effects, these results indicate that CO is a possible therapeutic tool for deceased-donor organ transplantation.…”

Section: Discussionmentioning

confidence: 99%

High-pressure carbon monoxide preserves rat kidney grafts from apoptosis and inflammation

Abe

Yazawa

Fujino

et al. 2017

Laboratory Investigation

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Renal ischemia-reperfusion (I/R) injury is unavoidable in kidney transplantation (KTx) and frequently influences both short-and long-term allograft survival. Carbon monoxide (CO) has attracted attention as a medical gas with anti-inflammatory and anti-apoptotic effects. We investigated a new strategy for organ preservation using ex vivo application of high-pressure CO in an experimental rat KTx model. We preserved kidney grafts using a high-pressure chamber filled with mixed gases composed of CO and O 2 . We found that cold I/R injury resulted in progressive deterioration of renal graft function in University of Wisconsin solution, whereas CO significantly improved renal function. We confirmed that CO decreased oxidative stress and mRNA expression of proinflammatory cytokines and inhibited tubular apoptosis in the early phases. Western blot analysis demonstrated that CO increased phosphatidylinositol-3 kinase and phosphorylation of Akt and p38 mitogen-activated protein kinase. Furthermore, CO significantly alleviated tubular injury scores and suppressed the development of interstitial fibrosis at 100 days after KTx. Thus, high-pressure mixed CO and O 2 gases successfully preserved rat kidney grafts for 24 h by protecting tubular epithelial cells from apoptosis and inhibiting inflammation.

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“…The observed inhibition of phenotypic DC maturation as a consequence of HO-1 induction (12) might be one of the major mechanisms explaining the observation that the application of CoPPIX in organ donors could lead to prolonged allogeneic graft survival in kidney (16,17), heart (18), and bone marrow transplantation (19). Additionally it has been demonstrated that treatment with CoPPIX to induce HO-1 ameliorated I/R injury (20,21) and that a single donor treatment with methylene chloride (MC) to induce CO ameliorated chronic allograft nephropathy, as reflected in the reduced number of donor-derived DCs (22). Recently, we demonstrated that CoPPIX-mediated induction of HO-1 in rat BMDCs matured with LPS resulted in reduced mRNA expression of MHC class II and costimulatory molecules.…”

Section: Inhibition Of Dendritic Cell Maturation and Function Is Indementioning

confidence: 99%

Inhibition of Dendritic Cell Maturation and Function Is Independent of Heme Oxygenase 1 but Requires the Activation of STAT3

Mashreghi

Klemz

Knosalla

et al. 2008

The Journal of Immunology

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The induction of heme oxygenase 1 (HO-1) by a single treatment with cobalt protoporphyrin (CoPPIX) protects against inflammatory liver failure and ischemia reperfusion injury after allotransplantation. In this context, the HO-1-mediated inhibition of donor-derived dendritic cell maturation and migration is discussed as one of the key events of graft protection. To investigate the poorly understood mechanism of CoPPIX-induced HO-1 activity in more detail, we performed gene expression analysis in murine liver, revealing the up-regulation of STAT3 after CoPPIX treatment. By using wild-type and HO-1-deficient dendritic cells we demonstrated that LPS-induced maturation is dependent on STAT3 phosphorylation and independent of HO-1 activity. In summary, our observations revise our understanding of the anti-inflammatory properties of HO-1 and highlight the immunomodulatory capacity of STAT3, which might be of further interest for targeting undesired immune responses, including ischemia reperfusion injury.

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Induction of Carbon Monoxide in Donor Animals Prior to Organ Procurement Reduces Graft Immunogenicity and Inhibits Chronic Allograft Dysfunction

Abstract: Donor treatment for the induction of CO reduced graft immunogenicity and inhibited chronic allograft nephropathy.

Cited by 36 publications

References 47 publications

Heme oxygenase and renal disease

Heme oxygenase and renal disease

High-pressure carbon monoxide preserves rat kidney grafts from apoptosis and inflammation

Inhibition of Dendritic Cell Maturation and Function Is Independent of Heme Oxygenase 1 but Requires the Activation of STAT3

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