PMA에 의한 중성구의 당섭취 기전 연구

Mechanism of Glucose Uptake on PMA Stimulated Neutrophils

  • 백진영 (삼성서울병원 핵의학과) ;
  • 고봉호 (삼성서울병원 핵의학과) ;
  • 유만길 (삼성서울병원 핵의학과) ;
  • 진광호 (삼성서울병원 핵의학과)
  • Paik, Jin-Young (Department of Nuclear Medicine, Samsung Medical Center) ;
  • Ko, Bong-Ho (Department of Nuclear Medicine, Samsung Medical Center) ;
  • Yoo, Man-Kil (Department of Nuclear Medicine, Samsung Medical Center) ;
  • Jin, Kwang-Ho (Department of Nuclear Medicine, Samsung Medical Center)
  • 발행 : 2007.12.31

초록

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 [18F]FDG uptake of stimulated neutrophils. Human neutrophils were stimulated by 100 ng/mL phorbol-myristate-acetate (PMA), and respiratory burst was measured by cumulative luminescence with lucigenin. [18F]FDG uptake and total hexokinase activity was measured 20 min after PMA stimulation in the presence or absence of soluble RGD peptides (200 g/mL) and/or the PI3K inhibitor wortmannin (200 nM). PMA induced a 71.70.9 fold increase in neutrophil oxygen intermediate generation. [18F]FDG uptake was increased to $194.6{\pm} 3.7%$ and hexokinase activity to $145.0{\pm}2.0%$ of basal levels (both p<0.0005). RGD peptides attenuated respiratory burst activation to $35.6{\pm}0.2%$ (p<0.005), but did not inhibit stimulated [18F]FDG uptake or hexokinase activity. In contrast, without affecting respiratory burst activation, wortmannin inhibited PMA stimulated [18F]FDG uptake to $66.9{\pm}1.6%$ and hexokinase activity to $81.0{\pm}4.2%$ (both P<0.0005), demonstrating its dependence on PI3K activity. Neither RGD nor wortmannin reversed the other's inhibitory effect on stimulated [18F]FDG uptake and hexokinase activity or respiratory burst, which suggests the involvement of distinct signaling pathways. Neutrophil [18F]FDG uptake is enhanced by PMA through a mechanism that requires PI3K activity but is independent of integrin receptor occupancy or respiratory burst activation.

키워드