Functional modulation of human monocytes derived DCs by anaphylatoxins C3a and C5a

Immunobiology. 2012 Jan;217(1):65-73. doi: 10.1016/j.imbio.2011.07.033. Epub 2011 Aug 5.

Abstract

Anaphylatoxins C3a and C5a are important modulators for dendritic cell activation and function in mice. In order to verify the significance of these observations in man, we have investigated the functional modulation of human monocytes derived DCs by C3a and C5a. Here we report that engagement of C3aR or C5aR on human monocytes derived DCs (moDCs) enhances the cell activation and their capacity for allostimulation. In addition, we show that intracellular production of cAMP is reduced and PI3K/AKT, ERK and NF-κB signalling is increased following stimulation with C3a or C5a, identifying intracellular signalling pathways that could convert cell surface C3aR and C5aR engagement into changes in moDC functions. Our data provide evidence that human DCs are equipped to react to C3a/C5a and undergo phenotypic change as well as functional modulation. Complement offers a potential route to modulate human DC function and regulate T cell mediated immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects*
  • Animals
  • Cell Differentiation / immunology
  • Complement C3a / immunology
  • Complement C3a / metabolism
  • Complement C3a / pharmacology*
  • Complement C5a / immunology
  • Complement C5a / metabolism
  • Complement C5a / pharmacology*
  • Cyclic AMP / biosynthesis
  • Cyclic AMP / immunology
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Inflammation / immunology*
  • Male
  • Mice
  • Monocytes / immunology
  • Monocytes / metabolism
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / immunology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / immunology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptor, Anaphylatoxin C5a / immunology
  • Receptor, Anaphylatoxin C5a / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology

Substances

  • Cytokines
  • NF-kappa B
  • Receptor, Anaphylatoxin C5a
  • Complement C3a
  • Complement C5a
  • Cyclic AMP
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt