Heme- and iron-activated macrophages in sickle cell disease: an updated perspective.
| Autor: | Navaneethabalakrishnan S; Iron Research Laboratory, Lindsley Kimball Research Institute, New York Blood Center., An X; Laboratory of Membrane Biology, Lindsley Kimball Research Institute, New York Blood Center., Vinchi F; Iron Research Laboratory, Lindsley Kimball Research Institute, New York Blood Center.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Current opinion in hematology [Curr Opin Hematol] 2024 Nov 01; Vol. 31 (6), pp. 275-284. Date of Electronic Publication: 2024 Jul 16. |
| DOI: | 10.1097/MOH.0000000000000836 |
| Abstrakt: | Purpose of Review: Sickle cell disease (SCD) is a hereditary blood disorder due to a single-point mutation in the β-globin gene. The ensuing hemoglobin has the tendency to polymerize upon deoxygenation, leading to the typical sickle shape of red blood cells. While the primary pathology of sickle cell disease is a direct consequence of altered red blood cells, emerging evidence highlights the central role of macrophages in mediating hemoglobin scavenging, perpetuating oxidative stress and inflammation, and causing endothelial dysfunction and tissue remodeling. Recent Findings: Recent research uncovered the impact of heme and iron overload on macrophage polarization and functions in sickle cell disease, and its implication for chronic inflammation and tissue damage in vital organs such as the liver, spleen, lungs and kidneys. By providing a thorough understanding of the dynamic interactions between macrophages and various cellular components within the sickle cell disease milieu, these studies have laid the foundation for the identification of macrophage-related cellular and molecular mechanisms potentially targetable for therapeutic purposes to attenuate sickle complications. Summary: This review provides a current update about recent discoveries on heme/iron-activated macrophages in SCD, shedding light on their critical role in disease pathophysiology. Ultimately, it proposes avenues for future research aimed at addressing the relevance of these cells for other sickle complications and at targeting them to mitigate disease morbidity and improve patient outcomes. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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