Extracellular NAD is a regulator for FcgammaR-mediated phagocytosis in murine macrophages

Biochem Biophys Res Commun. 2008 Feb 29;367(1):156-61. doi: 10.1016/j.bbrc.2007.12.131. Epub 2007 Dec 31.

Abstract

NAD is available in the extracellular environment and elicits immune modulation such as T cell apoptosis by being used as the substrate of cell surface ADP-ribosyl transferase. However, it is unclear whether extracellular NAD affects function of macrophages expressing cell surface ADP-ribosyl transferase. Here we show that extracellular NAD enhances Fcgamma receptor (FcgammaR)-mediated phagocytosis in J774A.1 macrophages via the conversion into cyclic ADP-ribose (cADPR), a potent calcium mobilizer, by CD38, an ADP-ribosyl cyclase. Extracellular NAD increased the phagocytosis of IgG-coated sheep red blood cells (IgG-SRBC) in J774A.1 macrophages, which was completely abolished by pretreatment of 8-bromo-cADPR, an antagonist of cADPR, or CD38 knockdown. Extracellular NAD increased basal intracellular Ca(2+) concentration, which also was abolished by pretreatment of 8-bromo-cADPR or CD38 knockdown. Moreover, the chelation of intracellular calcium abolished NAD-induced enhancement of phagocytosis of IgG-SRBC. Our results suggest that extracellular NAD act as a regulator for FcgammaR-mediated phagocytosis in macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Animals
  • Biological Transport
  • Calcium / metabolism*
  • Cells, Cultured
  • Cyclic ADP-Ribose / metabolism
  • Extracellular Space / metabolism*
  • Immunoglobulin G / blood
  • Macrophages / pathology
  • Macrophages / physiology*
  • Mice
  • NAD / metabolism*
  • Phagocytosis / physiology*
  • Receptors, IgG / metabolism*

Substances

  • Immunoglobulin G
  • Receptors, IgG
  • NAD
  • Cyclic ADP-Ribose
  • ADP-ribosyl Cyclase 1
  • Calcium