Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/ijms21030740
Keywords
BACH1; heme; heme-binding proteins; inflammation; macrophages
Funding
- Deutsche Forschungsgemeinschaft (DFG), Bonn (Germany) [IM 20/4-1]
- [03INT502AB]
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Macrophages are an integral part of the mononuclear phagocyte system that is critical for maintaining immune homeostasis. They play a key role for initiation and modulation of immunological responses in inflammation and infection. Moreover, macrophages exhibit a wide spectrum of tissue-specific phenotypes in steady-state and pathophysiological conditions. Recent clinical and experimental evidence indicates that the ubiquitous compound heme is a crucial regulator of these cells, e.g., in the differentiation of monocytes to tissue-resident macrophages and / or in activation by inflammatory stimuli. Notably, heme, an iron containing tetrapyrrole, is essential as a prosthetic group of hemoproteins (e.g., hemoglobin and cytochromes), whereas non-protein bound free or labile heme can be harmful via pro-oxidant, pro-inflammatory, and cytotoxic effects. In this review, it will be discussed how the complex interplay of heme with macrophages regulates homeostasis and inflammation via modulating macrophage inflammatory characteristics and/ or hematopoiesis. A particular focus will be the distinct roles of intra- and extracellular labile heme and the regulation of its availability by heme-binding proteins. Finally, it will be addressed how heme modulates macrophage functions via specific transcriptional factors, in particular the nuclear repressor BTB and CNC homologue (BACH)1 and Spi-C.
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