title: PMA-enhanced neutrophil [18F]FDG uptake is independent of integrin occupancy but requires PI3K activity.
abstract: OBJECTIVE
  While respiratory burst enhances neutrophil glucose utilization, many neutrophil functions are critically influenced by extracellular matrix interaction and phosphoinositide-3-OH kinase (PI3K) signaling. We thus evaluated the role of RGD integrin occupancy and PI3K inhibition on respiratory burst and [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake of stimulated neutrophils.
  
  
  METHODS
  Human neutrophils were stimulated by 100 ng/ml phorbol-myristate-acetate (PMA), and respiratory burst was measured by cumulative luminescence with lucigenin. [(18)F]FDG uptake and total hexokinase activity was measured 20 min after PMA stimulation in the presence or absence of soluble RGD peptides (200 microg/ml) and/or the PI3K inhibitor wortmannin (200 nM).
  
  
  RESULTS
  Phorbol-myristate-acetate induced a 71.7+/-0.9 fold increase in neutrophil oxygen intermediate generation. [(18)F]FDG uptake was increased to 194.6+/-3.7% and hexokinase activity to 145.0+/-2.0% of basal levels (both P<.0005). RGD peptides attenuated respiratory burst activation to 35.6+/-0.2% (P<.005) but did not inhibit stimulated [(18)F]FDG uptake or hexokinase activity. In contrast, without affecting respiratory burst activation, wortmannin inhibited PMA-stimulated [(18)F]FDG uptake to 66.9+/-1.6% and hexokinase activity to 81.0+/-4.2% (both P<.0005), demonstrating its dependence on PI3K activity. Neither RGD nor wortmannin reversed the other's inhibitory effect on stimulated [(18)F]FDG uptake and hexokinase activity or respiratory burst, which suggests the involvement of distinct signaling pathways.
  
  
  CONCLUSIONS
  Neutrophil [(18)F]FDG uptake is enhanced by PMA through a mechanism that requires PI3K activity but is independent of integrin receptor occupancy or respiratory burst activation.
authors: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
authors: Jin-Young
authors: JY
authors: Paik
authors: Bong-Ho
authors: BH
authors: Ko
authors: Yearn Seong
authors: YS
authors: Choe
authors: Yong
authors: Y
authors: Choi
authors: Kyung-Han
authors: KH
authors: Lee
authors: Byung-Tae
authors: BT
authors: Kim
mesh_terms: D000166:Acridines; D000730:Androstadienes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008163:Luminescent Measurements; D009504:Neutrophils / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014055:Tomography, Emission-Computed; D000077191:Wortmannin
chemical_list: D000166:Acridines; D000730:Androstadienes; D000970:Antineoplastic Agents; D002273:Carcinogens; D019788:Fluorodeoxyglucose F18; D006593:Hexokinase; D016023:Integrins; D009842:Oligopeptides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D019275:Radiopharmaceuticals; D011971:Receptors, Immunologic; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin; C033472:10,10'-dimethyl-9,9'-biacridinium; C047981:arginyl-glycyl-aspartic acid