Modulation of macrophage differentiation and activation by decoy receptor 3

J Leukoc Biol. 2004 Mar;75(3):486-94. doi: 10.1189/jlb.0903448. Epub 2003 Dec 4.

Abstract

Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily and is readily detected in certain cancer patients. Recently, we demonstrated that DcR3.Fc-treated dendritic cells skew T cell responses to a T helper cell type 2 phenotype. In this study, we further asked its ability to modulate CD14+ monocyte differentiation into macrophages induced by macrophage-colony stimulating factor in vitro. We found that DcR3.Fc was able to modulate the expression of several macrophage markers, including CD14, CD16, CD64, and human leukocyte antigen-DR. In contrast, the expression of CD11c, CD36, CD68, and CD206 (mannose receptor) was not affected in the in vitro culture system. Moreover, phagocytic activity toward immune complexes and apoptotic bodies as well as the production of free radicals and proinflammatory cytokines in response to lipopolysaccharide were impaired in DcR3.Fc-treated monocyte-derived macrophages. This suggests that DcR3.Fc might have potent, suppressive effects to down-regulate the host-immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • Cell Differentiation / drug effects
  • Drug Interactions
  • Free Radicals / metabolism
  • Humans
  • Jurkat Cells
  • Lipopolysaccharide Receptors
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Membrane Glycoproteins / pharmacology*
  • Monocytes / cytology
  • Monocytes / drug effects
  • Phagocytosis / drug effects
  • Receptors, Cell Surface
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 6b
  • Recombinant Fusion Proteins / pharmacology

Substances

  • Antigens, CD
  • Free Radicals
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 6b
  • Recombinant Fusion Proteins
  • TNFRSF6B protein, human
  • Macrophage Colony-Stimulating Factor