Regulation of CD163 on human macrophages: cross‐linking of CD163 induces signaling and activation

CD163 is a member of the group B scavenger receptor cysteine‐rich (SRCR) superfamily. This study describes aspects of the tissue distribution, the regulation of expression, and signal transduction after cross‐linking of this receptor at the cell surface of macrophages. CD163 showed an exclusive expression on resident macrophages (e.g., red pulp macrophages, alveolar macrophages). The expression was inducible on monocyte‐derived macrophages by glucocorticoids but not by interleukin‐4 (IL‐4), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and interferon‐γ. The combination of IL‐4 or GM‐CSF with glucocorticoids resulted in a further increase. Subcellular analysis of alveolar macrophages by immunoelectron microscopy showed a plasma membrane localization of the antigen. Cross‐linking of CD163 with monoclonal antibody induced a protein tyrosine kinase‐dependent signal that resulted in (1) slow‐type calcium mobilization, (2) inositol triphosphate production, and (3) secretion of IL‐6 and GM‐CSF. The data suggest a function for the SRCR‐superfamily receptor CD163 in the regulation of inflammatory processes by macrophages. J. Leukoc. Biol. 66: 858–866; 1999.