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KMID : 1101320070390030249
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Korean Journal of Clinical Laboratory Science
2007 Volume.39 No. 3 p.249 ~ p.255
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Mechanism of Glucose Uptake on PMA Stimulated Neutrophils
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Paik Jin-Young
Ko Bong-Ho
Yoo Man-Kil
Jin Kwang-Ho
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Abstract
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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± 3.7% and hexokinase activity to 145.0± 2.0% of basal levels (both p<0.0005). RGD peptides attenuated respiratory burst activation to 35.6± 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± 1.6% and hexokinase activity to 81.0± 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.
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KEYWORD
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Neutrophil, [18F]FDG, Respiratory burst, RGD
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