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

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.