Extracellular NAD is a regulator for FcgammaR-mediated phagocytosis in murine macrophages.
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.
Song
Eun-Kyung
EK
Department of Microbiology and Immunology, Chonbuk National University Medical School, Jeonju 561-182, South Korea.
Lee
Young-Rae
YR
Yu
Hong-Nu
HN
Kim
Uh-Hyun
UH
Rah
So-Young
SY
Park
Kwang-Hyun
KH
Shim
In-Kyung
IK
Lee
Seung-Jin
SJ
Park
Yeong-Min
YM
Chung
Weon-Guu
WG
Kim
Jong-Suk
JS
Han
Myung-Kwan
MK
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D051379:Mice; D009243:NAD / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D017452:Receptors, IgG / Q000378:metabolism*
D007074:Immunoglobulin G; D017452:Receptors, IgG; D009243:NAD; D036563:Cyclic ADP-Ribose; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium