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

Abstract

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 colonystimulating factor (GM-CSF), and interferon-␥. 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 SRCRsuperfamily receptor CD163 in the regulation of inflammatory processes by macrophages. J. Leukoc. Biol. 66: 858-866; 1999.

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

“…In contrast to previous reports that used Hb contaminated with endotoxin (138,176), these macrophages are characterized by an anti-inflammatory gene expression profile and a unique three-gene signature of increased hmox-1 and glutamate-cysteine ligase modified (gclm) and suppressed [d]-aminolevulinate synthase (alas1), the rate-limiting enzyme in heme synthesis (142). This gene expression profile clearly distinguishes heme-induced CD163 + macrophages from the M1 or M2 macrophage subsets.…”

Human peritoneal macrophages show functional characteristics of M‐CSF‐driven anti‐inflammatory type 2 macrophages

“…The following mAb were used for flow cytometry analysis to analyze the surface molecules on different MU: anti-DC-SIGN/ CD209 (AZN-D1; a gift of Dr. Y. van Kooyk, VU Medical Center, Amsterdam, The Netherlands), anti-CD86 (IT2.2; Pharmingen, San Diego, CA), anti-CD16 (3G8; a gift from Dr. J. G. J. van de Winkel, University of Utrecht, Utrecht, The Netherlands) and anti-CD163 (EDhu1, [22]). Staining was visualized by PEconjugated goat anti-mouse Ig (Dako, Glostrup, Denmark) and compared to appropriate isotype controls.…”

α1-Acid Glycoprotein Up-regulates CD163 via TLR4/CD14 Protein Pathway

“…For example, a genomic analysis of the CD163 promoter region revealed the presence of several binding sites for transcription factors in the 5Ј-flanking region (45), including three putative glucocorticoid receptor binding sites. In fact, monocytes that had been treated with glucocorticoids or derived from patients on glucocorticoid pulse therapy showed a strongly induced CD163 expression (12,15,46,47). Taking the collective findings into consideration, with the evidence that glucocorticoid also up-regulates AGP synthesis (20), glucocorticoids might not only regulate CD163 expression directly but also indirectly via enhancing AGP production.…”

“…For example, anti-inflammatory mediators such as glucocorticoids and IL-10 are particularly potent inducers (12)(13)(14). However, this is not a common feature of all anti-inflammatory cytokines because IL-4 and IL-13 do not cause an increase in CD163 expression (15,16). In contrast, pro-inflammatory cytokines (TNF-␣ and IFN-␥) and the chemokine CXCL4 suppress CD163 expression (12,16,17).…”