Song Eun-Kyung, Lee Young-Rae, Yu Hong-Nu, Kim Uh-Hyun, Rah So-Young, Park Kwang-Hyun, Shim In-Kyung, Lee Seung-Jin, Park Yeong-Min, Chung Weon-Guu, Kim Jong-Suk, Han Myung-Kwan
Department of Microbiology and Immunology, Chonbuk National University Medical School, Jeonju 561-182, South Korea.
Biochem Biophys Res Commun. 2008 Feb 29;367(1):156-61. doi: 10.1016/j.bbrc.2007.12.131. Epub 2007 Dec 31.
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.
NAD存在于细胞外环境中，并通过作为细胞表面ADP-核糖基转移酶的底物引发免疫调节，如T细胞凋亡。然而，细胞外NAD是否影响表达细胞表面ADP-核糖基转移酶的巨噬细胞功能尚不清楚。在这里，我们表明细胞外NAD通过ADP-核糖基环化酶CD38转化为环状ADP-核糖（cADPR，一种有效的钙动员剂），增强J774A.1巨噬细胞中Fcγ受体（FcγR）介导的吞噬作用。细胞外NAD增加了J774A.1巨噬细胞中IgG包被的绵羊红细胞（IgG-SRBC）的吞噬作用，而cADPR拮抗剂8-溴-cADPR预处理或CD38基因敲低可完全消除这种作用。细胞外NAD增加了基础细胞内Ca(2+)浓度，8-溴-cADPR预处理或CD38基因敲低也可消除这种作用。此外，细胞内钙螯合消除了NAD诱导的IgG-SRBC吞噬作用增强。我们的结果表明，细胞外NAD在巨噬细胞中作为FcγR介导的吞噬作用的调节剂。
