PMID- 11994530
OWN - NLM
STAT- MEDLINE
DCOM- 20020523
LR  - 20181130
IS  - 0161-5505 (Print)
IS  - 0161-5505 (Linking)
VI  - 43
IP  - 5
DP  - 2002 May
TI  - Dissociation between respiratory burst activity and deoxyglucose uptake in human 
      neutrophil granulocytes: implications for interpretation of (18)F-FDG PET images.
PG  - 652-7
AB  - 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 (18)F-FDG after intravenous injection. METHODS: To 
      understand the mechanism responsible for the increased (18)F-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 (3)H-DG uptake are temporally dissociated, that neutrophil-priming 
      agents such as tumor necrosis factor-alpha (TNFalpha) cause an identical increase 
      in (3)H-DG uptake compared with fMLP without affecting respiratory burst 
      activity, and that fMLP stimulation of TNFalpha-primed cells causes major 
      upregulation of superoxide anion generation (O(2)(-)) yet no incremental increase 
      in (3)H-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 (3)H-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 TNFalpha- or fMLP-stimulated (3)H-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 (3)H-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 (18)F-FDG 
      signals in vivo.
FAU - Jones, Hazel A
AU  - Jones HA
AD  - Respiratory Medicine Division, Department of Medicine, University of Cambridge 
      School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Cambridge, 
      United Kingdom. hazel.jones@ic.ac.uk
FAU - Cadwallader, Karen A
AU  - Cadwallader KA
FAU - White, Jessica F
AU  - White JF
FAU - Uddin, Mohib
AU  - Uddin M
FAU - Peters, A Michael
AU  - Peters AM
FAU - Chilvers, Edwin R
AU  - Chilvers ER
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Nucl Med
JT  - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JID - 0217410
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Deoxyglucose/*metabolism
MH  - *Fluorodeoxyglucose F18
MH  - Humans
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*metabolism
MH  - Peroxidase/metabolism
MH  - *Respiratory Burst
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - *Tomography, Emission-Computed
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2002/05/08 10:00
MHDA- 2002/05/25 10:01
CRDT- 2002/05/08 10:00
PHST- 2002/05/08 10:00 [pubmed]
PHST- 2002/05/25 10:01 [medline]
PHST- 2002/05/08 10:00 [entrez]
PST - ppublish
SO  - J Nucl Med. 2002 May;43(5):652-7.