Dissociation Between Respiratory Burst Activity and Deoxyglucose Uptake in Human Neutrophil Granulocytes: Implications for Interpretation of 18F-FDG PET Images

Journal of Nuclear Medicine

Edwin R. Chilvers¹  Karen A. Cadwallader¹  A. Michael Peters¹  Jessica F. White¹  Hazel A. Jones¹  Mohib Uddin¹ 

关键词: FDG;    PET;    neutrophils;    respiratory burst;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Neutrophil granulocytes play a key role in the pathogenesis of a wide variety of pulmonary diseases. In many such conditions, the injury observed reflects the activation status rather than the total number of inflammatory cells present. The metabolic activity of neutrophils can now be assessed noninvasively using PET to measure the regional uptake of 18F-FDG after intravenous injection. Methods: To understand the mechanism responsible for the increased 18F-FDG signal, we have measured the uptake of tritiated deoxyglucose (DG) in neutrophils isolated from human peripheral blood and sought to determine which aspects of neutrophil function correlate with an increase in DG uptake. Results: Our results show that formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated respiratory burst activity and 3H-DG uptake are temporally dissociated, that neutrophil-priming agents such as tumor necrosis factor-α (TNFα) cause an identical increase in 3H-DG uptake compared with fMLP without affecting respiratory burst activity, and that fMLP stimulation of TNFα-primed cells causes major upregulation of superoxide anion generation (O2−) yet no incremental increase in 3H-DG uptake. Furthermore, direct activation of reduced nicotinamide adenine dinucleotide phosphate oxidase activity with the ester phorbol 12-myristate 13-acetate resulted in a concentration-dependent loss of cell-associated 3H-DG, and preincubation of neutrophils with the phosphoinositide 3-kinase inhibitor wortmannin, which abolished both agonist-stimulated superoxide anion generation and degranulation, had no effect on TNFα- or fMLP-stimulated 3H-DG uptake. In contrast, the fMLP-stimulated change in neutrophil shape was not influenced by priming or wortmannin, and of the functional responses examined, this appeared to correlate most closely with 3H-DG uptake. Conclusion: DG uptake occurs in both primed and activated neutrophils. It does not correlate with respiratory burst or secretory activity but may reflect the polarization and migrational status of these cells. These data have important implications for the analysis of 18F-FDG signals in vivo.

【 授权许可】

Unknown