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The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease
Hemolysis is a pathological feature of several diseases of diverse etiology such as hereditary anemias, malaria, and sepsis. A major complication of hemolysis involves the release of large quantities of hemoglobin into the blood circulation and the subsequent generation of harmful metabolites like l...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873693/ https://www.ncbi.nlm.nih.gov/pubmed/33584641 http://dx.doi.org/10.3389/fimmu.2020.561917 |
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author | Gbotosho, Oluwabukola T. Kapetanaki, Maria G. Kato, Gregory J. |
author_facet | Gbotosho, Oluwabukola T. Kapetanaki, Maria G. Kato, Gregory J. |
author_sort | Gbotosho, Oluwabukola T. |
collection | PubMed |
description | Hemolysis is a pathological feature of several diseases of diverse etiology such as hereditary anemias, malaria, and sepsis. A major complication of hemolysis involves the release of large quantities of hemoglobin into the blood circulation and the subsequent generation of harmful metabolites like labile heme. Protective mechanisms like haptoglobin-hemoglobin and hemopexin-heme binding, and heme oxygenase-1 enzymatic degradation of heme limit the toxicity of the hemolysis-related molecules. The capacity of these protective systems is exceeded in hemolytic diseases, resulting in high residual levels of hemolysis products in the circulation, which pose a great oxidative and proinflammatory risk. Sickle cell disease (SCD) features a prominent hemolytic anemia which impacts the phenotypic variability and disease severity. Not only is circulating heme a potent oxidative molecule, but it can act as an erythrocytic danger-associated molecular pattern (eDAMP) molecule which contributes to a proinflammatory state, promoting sickle complications such as vaso-occlusion and acute lung injury. Exposure to extracellular heme in SCD can also augment the expression of placental growth factor (PlGF) and interleukin-6 (IL-6), with important consequences to enthothelin-1 (ET-1) secretion and pulmonary hypertension, and potentially the development of renal and cardiac dysfunction. This review focuses on heme-induced mechanisms that are implicated in disease pathways, mainly in SCD. A special emphasis is given to heme-induced PlGF and IL-6 related mechanisms and their role in SCD disease progression. |
format | Online Article Text |
id | pubmed-7873693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78736932021-02-11 The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease Gbotosho, Oluwabukola T. Kapetanaki, Maria G. Kato, Gregory J. Front Immunol Immunology Hemolysis is a pathological feature of several diseases of diverse etiology such as hereditary anemias, malaria, and sepsis. A major complication of hemolysis involves the release of large quantities of hemoglobin into the blood circulation and the subsequent generation of harmful metabolites like labile heme. Protective mechanisms like haptoglobin-hemoglobin and hemopexin-heme binding, and heme oxygenase-1 enzymatic degradation of heme limit the toxicity of the hemolysis-related molecules. The capacity of these protective systems is exceeded in hemolytic diseases, resulting in high residual levels of hemolysis products in the circulation, which pose a great oxidative and proinflammatory risk. Sickle cell disease (SCD) features a prominent hemolytic anemia which impacts the phenotypic variability and disease severity. Not only is circulating heme a potent oxidative molecule, but it can act as an erythrocytic danger-associated molecular pattern (eDAMP) molecule which contributes to a proinflammatory state, promoting sickle complications such as vaso-occlusion and acute lung injury. Exposure to extracellular heme in SCD can also augment the expression of placental growth factor (PlGF) and interleukin-6 (IL-6), with important consequences to enthothelin-1 (ET-1) secretion and pulmonary hypertension, and potentially the development of renal and cardiac dysfunction. This review focuses on heme-induced mechanisms that are implicated in disease pathways, mainly in SCD. A special emphasis is given to heme-induced PlGF and IL-6 related mechanisms and their role in SCD disease progression. Frontiers Media S.A. 2021-01-27 /pmc/articles/PMC7873693/ /pubmed/33584641 http://dx.doi.org/10.3389/fimmu.2020.561917 Text en Copyright © 2021 Gbotosho, Kapetanaki and Kato http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Gbotosho, Oluwabukola T. Kapetanaki, Maria G. Kato, Gregory J. The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease |
title | The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease |
title_full | The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease |
title_fullStr | The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease |
title_full_unstemmed | The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease |
title_short | The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease |
title_sort | worst things in life are free: the role of free heme in sickle cell disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873693/ https://www.ncbi.nlm.nih.gov/pubmed/33584641 http://dx.doi.org/10.3389/fimmu.2020.561917 |
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