title: Scant Extracellular NAD Cleaving Activity of Human Neutrophils is Down-Regulated by fMLP via FPRL1.
abstract: Extracellular nicotinamide adenine dinucleotide (NAD) cleaving activity of a particular cell type determines the rate of the degradation of extracellular NAD with formation of metabolites in the vicinity of the plasma membrane, which has important physiological consequences. It is yet to be elucidated whether intact human neutrophils have any extracellular NAD cleaving activity. In this study, with a simple fluorometric assay utilizing 1,N(6)-ethenoadenine dinucleotide (etheno-NAD) as the substrate, we have shown that intact peripheral human neutrophils have scant extracellular etheno-NAD cleaving activity, which is much less than that of mouse bone marrow neutrophils, mouse peripheral neutrophils, human monocytes and lymphocytes. With high performance liquid chromatography (HPLC), we have identified that ADP-ribose (ADPR) is the major extracellular metabolite of NAD degradation by intact human neutrophils. The scant extracellular etheno-NAD cleaving activity is decreased further by N-formyl-methionine-leucine-phenylalanine (fMLP), a chemoattractant for neutrophils. The fMLP-mediated decrease in the extracellular etheno-NAD cleaving activity is reversed by WRW4, a potent FPRL1 antagonist. These findings show that a much less extracellular etheno-NAD cleaving activity of intact human neutrophils compared to other immune cell types is down-regulated by fMLP via a low affinity fMLP receptor FPRL1.
authors.affiliation: Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Md Ashraful
authors.initials: MA
authors.lastname: Hasan
authors.affiliation: Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Md Tipu
authors.initials: MT
authors.lastname: Sultan
authors.affiliation: Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Won-Gyun
authors.initials: WG
authors.lastname: Ahn
authors.affiliation: Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Yeon-Ja
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Chang-Won
authors.initials: CW
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Dong-Keun
authors.initials: DK
authors.lastname: Song
keywords: Extracellular NAD cleaving activity; FPRL1; Human neutrophils; fMLP