Induction of the CD163‐dependent haemoglobin uptake by macrophages as a novel anti‐inflammatory action of glucocorticoids

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Abstract
Summary. Highly efficient systems remove toxic and pro‐inflammatory haemoglobin (Hb) from the circulation and local sites of tissue damage. Macrophages are major Hb‐clearing cells; CD163 was recently recognized as the specific haemoglobin–haptoglobin scavenger receptor (HSR). We show that dexamethasone strongly induced the specific uptake of haemoglobin–haptoglobin complexes, CD163 mRNA transcription (13‐fold) and cell surface expression (10‐fold) by human macrophages. In contrast, the TH2‐cytokine interleukin 4 (IL‐4) completely suppressed functional CD163 expression. The range of functional receptor modulation reached a factor of 100 after 4 h of macrophage–ligand interaction. Based on these results, we propose the augmentation of Hb clearance as a novel anti‐inflammatory action of glucocorticoids.