Regulation of CD 163 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-gamma. 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.
Van den Heuvel
M M
MM
Department of Cell Biology & Immunology, Faculty of Medicine, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands.
Tensen
C P
CP
van As
J H
JH
Van den Berg
T K
TK
Fluitsma
D M
DM
Dijkstra
C D
CD
Döpp
E A
EA
Droste
A
A
Van Gaalen
F A
FA
Sorg
C
C
Högger
P
P
Beelen
R H
RH
D000818:Animals; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D015151:Immunoblotting; D007424:Intracellular Fluid; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D003432:Cross-Linking Reagents; D016207:Cytokines; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger