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The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex...

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Autores principales: Thomsen, Jens Haugbølle, Etzerodt, Anders, Svendsen, Pia, Moestrup, Søren K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678498/
https://www.ncbi.nlm.nih.gov/pubmed/23781295
http://dx.doi.org/10.1155/2013/523652
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author Thomsen, Jens Haugbølle
Etzerodt, Anders
Svendsen, Pia
Moestrup, Søren K.
author_facet Thomsen, Jens Haugbølle
Etzerodt, Anders
Svendsen, Pia
Moestrup, Søren K.
author_sort Thomsen, Jens Haugbølle
collection PubMed
description The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex in macrophages followed by lysosomal Hp-Hb breakdown and HO-1-catalyzed conversion of heme into the metabolites carbon monoxide (CO), biliverdin, and iron. The plasma concentration of Hp is a limiting factor as evident during accelerated hemolysis, where the Hp depletion may cause serious Hb-induced toxicity and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6), but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway in the anti-inflammatory response.
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spelling pubmed-36784982013-06-18 The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging Thomsen, Jens Haugbølle Etzerodt, Anders Svendsen, Pia Moestrup, Søren K. Oxid Med Cell Longev Review Article The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex in macrophages followed by lysosomal Hp-Hb breakdown and HO-1-catalyzed conversion of heme into the metabolites carbon monoxide (CO), biliverdin, and iron. The plasma concentration of Hp is a limiting factor as evident during accelerated hemolysis, where the Hp depletion may cause serious Hb-induced toxicity and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6), but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway in the anti-inflammatory response. Hindawi Publishing Corporation 2013 2013-05-27 /pmc/articles/PMC3678498/ /pubmed/23781295 http://dx.doi.org/10.1155/2013/523652 Text en Copyright © 2013 Jens Haugbølle Thomsen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Thomsen, Jens Haugbølle
Etzerodt, Anders
Svendsen, Pia
Moestrup, Søren K.
The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging
title The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging
title_full The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging
title_fullStr The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging
title_full_unstemmed The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging
title_short The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging
title_sort haptoglobin-cd163-heme oxygenase-1 pathway for hemoglobin scavenging
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678498/
https://www.ncbi.nlm.nih.gov/pubmed/23781295
http://dx.doi.org/10.1155/2013/523652
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