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.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods; D006242:Haptoglobins / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000098902:CD163 Antigen
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D011956:Receptors, Cell Surface; D003907:Dexamethasone