Interplay of Heme with Macrophages in Homeostasis and Inflammation
Abstract
:1. Introduction
2. The Intra- and Extracellular Pool of Labile Heme
3. Role of Extra- and Intra-Cellular Heme-Binding Proteins (HBPs) in the Regulation of Labile Heme Homeostasis
3.1. Extracellular HBPs Neutralize Labile Heme
3.2. Intracellular HBPs Regulate Bioavailability of Labile Heme
3.3. Intracellular Labile Heme Controls Cellular Functions via Heme-Sensor Proteins
4. How Heme and Macrophages Control Erythropoiesis in Steady State and during Inflammation?
Heme Sustains Erythropoiesis through Differentiation of Erythrophagocytosing Macrophages
5. Role of Heme in Inflammatory Activation of Macrophages
5.1. Heme as an Anti-Inflammatory Signal in Macrophages
5.2. Heme as a Pro-Inflammatory Signal in Macrophages
6. Conclusions and Outlook
Funding
Conflicts of Interest
References
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Heme Binding Protein | Heme Affinity (Kd) (M) | Serum Concentration | Ref. |
---|---|---|---|
Hemopexin | 1 × 10−14 | 0.6–1.2 g/L | [38,43] |
Albumin | 1.2 × 10−8 | 35–53 g/L | [39,44] |
α1-Microglobulin | 1 × 10−6 | 0.03 g/L | [41] |
α1-Antitrypsin | 2 × 10−8 | 1.3–2.5 g/L | [42] |
Heme binding protein | Function | Ref |
---|---|---|
Putative heme transporters | ||
Feline leukemia virus subgroup C receptor 1a (FLVCR1a) | export of heme to extracellular space | [48,50] |
Feline leukemia virus subgroup C receptor 1a (FLVCR1b) | export of heme from the mitochondria to cytosol | [51] |
Feline leukemia virus subgroup C receptor 2 (FLVCR2) | import of heme from extracellular space | [52] |
Heme responsive gene-1 (HRG-1) | export of heme from phagolysosome to cytosol | [46] |
Heme carrier protein-1 (HCP-1) | export of heme from lysosome to cytosol (?) | [47] |
Putative heme chaperones | ||
Biliverdin reductase (BVR) | heme trafficking to nucleus (?) | [53] |
Fatty acid binding protein (FABP) | heme trafficking in cytosol (?) | [54] |
Glceraldehyde phosphate dehydrogenase (GAPDH) | heme trafficking in cytosol | [22], [55] |
GSH-S-transferase | heme trafficking in cytosol (?) | [56] |
Heme binding protein 22 (HBP22) | heme trafficking in cytosol (?) | [57] |
Heme binding protein 23 (HBP23) | heme trafficking in cytosol (?) | [58] |
SOUL | heme trafficking in cytosol (?) | [59] |
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Pradhan, P.; Vijayan, V.; Gueler, F.; Immenschuh, S. Interplay of Heme with Macrophages in Homeostasis and Inflammation. Int. J. Mol. Sci. 2020, 21, 740. https://doi.org/10.3390/ijms21030740
Pradhan P, Vijayan V, Gueler F, Immenschuh S. Interplay of Heme with Macrophages in Homeostasis and Inflammation. International Journal of Molecular Sciences. 2020; 21(3):740. https://doi.org/10.3390/ijms21030740
Chicago/Turabian StylePradhan, Pooja, Vijith Vijayan, Faikah Gueler, and Stephan Immenschuh. 2020. "Interplay of Heme with Macrophages in Homeostasis and Inflammation" International Journal of Molecular Sciences 21, no. 3: 740. https://doi.org/10.3390/ijms21030740