In vivo measurement of neutrophil activity in experimental lung inflammation.

Abstract

Positron emission tomography (PET) was used to quantify 18fluorodeoxyglucose (18FDG) uptake in rabbits with experimental pneumonitis localized to the right upper lobe. In Streptococcus pneumoniae-induced pneumonia, which causes a profound inflammatory response lasting several days before it resolves, 18FDG uptake was pronounced at 15 h after the onset of inflammation, but by 48 h there was little uptake. In bleomycin injury, which progresses from an acute inflammatory stage to chronic inflammation and scarring, 18FDG uptake detectable by PET persisted for up to 21 d. Autoradiography of histologic sections after intravenous administration of [3H]deoxyglucose 15 h after streptococcal instillation and 2 wk after bleomycin instillation showed that, in both models, deoxyglucose uptake was localized to neutrophils. In the streptococcal model there was little 18FGD signal at 6 h, when major neutrophil migration occurs. At 15 h, [3H]deoxyglucose-labeled neutrophils were present in the airspaces but not in the alveolar septa, suggesting that the deoxyglucose signal reflected a postmigratory neutrophil event, probably the respiratory burst. Thus, PET of 18FDG uptake may provide a novel and readily repeatable, noninvasive approach to the in vivo study of neutrophil activity at otherwise inaccessible sites.

Evaluation of allergic lung inflammation by computed tomography in a rat modelin vivo

“…A number of imaging technologies are currently available to evaluate lung inflammation but the application of these techniques to allergic inflammation is limited. For example, 18 F-fluorodeoxyglucose, in conjunction with positron emission tomography (PET), is commonly used to assess increased glucose uptake, and therefore metabolism, as a surrogate of inflammatory cell activity [14]. Unfortunately, this technique has not been shown to be a useful assessment of airway inflammation in asthmatics [15], unless under conditions of a segmental allergen challenge [16,17], most likely because neutrophils, a cell-type with a debatable association to allergic asthma, use more glucose than other cell types when activated [18,19].…”

“…For example, 18 F-fluorodeoxyglucose, in conjunction with positron emission tomography (PET), is commonly used to assess increased glucose uptake, and therefore metabolism, as a surrogate of inflammatory cell activity [14]. Unfortunately, this technique has not been shown to be a useful assessment of airway inflammation in asthmatics [15], unless under conditions of a segmental allergen challenge [16,17], most likely because neutrophils, a cell-type with a debatable association to allergic asthma, use more glucose than other cell types when activated [18,19]. Magnetic resonance imaging has also been used to detect inflammatory changes [20][21][22] as well as functional disruption after allergen exposure [23] in experimental models of asthma.…”

Inflammatory neutrophils retain susceptibility to apoptosis mediated via the Fas death receptor

“…The lifespan of the peripheral blood neutrophil is short, with a half-life of 6-8 h in vivo [40]. There is some in vivo evidence that the ''time-clock'' of neutrophil apoptosis can be modulated at inflamed sites, with extended survival of neutrophils that have migrated into skin windows [17] or into the lung, as assessed by positron emission tomography [16] or using cells harvested by bronchoalveolar lavage [19]. It is not clear, however, whether this altered survival at inflamed sites is due to resetting of the endogenous time-clock of apoptosis or to survival signals from the inflammatory milieu that are mediated via cell-surface receptors.…”

Modeling Pulmonary Kinetics of 2-Deoxy-2-[18F]fluoro-d-glucose During Acute Lung Injury

“…Recently, PET imaging of the glucose analog 2-deoxy-2-[ 18 F]fluoro-D-glucose ( 18 F-FDG), a standard tool in oncology, is increasingly used to assess metabolic activity of pulmonary inflammatory cells (4)(5)(6)(7)(8)(9)(10)(11). Such measurement is based on the fact that 18 F-FDG is phosphorylated and trapped in activated pulmonary neutrophils in proportion to the cells' glucose uptake, which is much higher than that of lung parenchyma.…”