Indium-111-Labelled Granulocyte Accumulation in Respiratory Tract of Patients With Bronchiectasis

Currie, D C; Peters, A. M.; George, Phillip; Lavender, J. P.; Saverymuttu, S. H.; Needham, S.G.; Dhillon, D P; Cole, P J

doi:10.1016/s0140-6736(87)90647-7

Cited by 59 publications

(28 citation statements)

References 19 publications

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“…The group also measured neutrophil activity by PET and injected 18 FDG. Neutrophil emigration was evident in four of the five bronchiectatic patients they examined, a finding similar to other studies [35,36]. Despite the ongoing neutrophil migration into the lungs, minimal neutrophil metabolic activity was detected by 18 FDG-PET imaging in bronchiectatic patients.…”

Section: Discussionsupporting

confidence: 86%

Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Labiris¹,

Nahmias²,

Freitag³

et al. 2003

Eur Respir J

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Positron emission tomography is a three-dimensional imaging technique that measures physiological effects, including metabolism. 18 Fluorodeoxyglucose has been extensively used as a tracer of cellular energy metabolism in the brain and in tumour detection. As neutrophils utilise glucose as an energy source during their respiratory burst, it was hypothesised that 18 fluorodeoxyglucose uptake, by these cells, could be interpreted as a measure of neutrophil activation in cystic fibrosis (CF).Ten adult CF patients were given a bolus intravenous injection of 18 fluorodeoxyglucose, followed by a 90-min dynamic mid-lung acquisition scan. Right-lung 18 fluorodeoxyglucose uptake was assessed using a Patlak plot and values were converted to glucose utilisation. Three clinically inactive pulmonary sarcoidosis patients served as controls.From the 10 CF patients with baseline sputum neutrophils of 14610 6 cells?mL -1 who were investigated, seven were found to have sputum at a normal or slightly depressed glucose utilisation rate (mean 1.33 mmol?g Positron emission tomography (PET) is a powerful, quantitative, nuclear medicine tomographic imaging technique. PET can be used to measure physiological effects such as blood flow, metabolism, ventilation, receptor occupancy, regional dose delivery and pharmacokinetics of radiolabelled drugs [1]. It combines principles of image reconstruction from projections with the use of specific biological molecules labelled with positron-emitting radioisotopes ( 11 C, 18 F, 15 O, 13 N) allowing regional measurements of dynamic processes to be taken. 18 FDG differs from glucose by the substitution of the hydroxyl group with a fluorine atom on the second carbon of the glucose. When injected intravenously, 18 FDG rapidly diffuses into the extracellular spaces throughout the body. It is transported into living cells by the same mechanism as glucose, via the D-glucose transporter and is phosphorylated by hexokinase to fluoro-deoxyglucose-6-phosphate. The deoxy substitution at the second carbon position prevents further metabolism and the product accumulates in the cell at a rate that reflects glucose metabolism. Increased glucose consumption is assumed to lead to an increased rate of tracer uptake. The rate of accumulation of 18 FDG in tissue after intravenous injection reflects the combined transport and hexokinase activity in the cells [9].18 FDG-PET studies of the lung are still relatively few compared with the number of oncological, neurological and cardiac studies.The inflammatory process, in particular neutrophils, has been implicated in the pathogenesis of a variety of lung diseases including cystic fibrosis (CF), bronchiectasis, and chronic bronchitis. Neutrophils contribute to pulmonary destruction by production and release of cytotoxic enzymes (e.g. elastase, myeloperoxidase) and toxic oxygen metabolites [10]. Markers of inflammation in blood, bronchoalveolar lavage (BAL), sputum and lung biopsy serve as indirect measurements of inflammation, making the detection of re...

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Section: Discussionsupporting

confidence: 86%

Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Labiris¹,

Nahmias²,

Freitag³

et al. 2003

Eur Respir J

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“…Neutrophils migrate from the bloodstream across vascular endothelium and smooth muscle to vascular sites of inflammation, play an important role in host defenses during tissue injury and inflammation, and also play an important role in tissue remodeling after injury (17,18). Current concepts suggest that neutrophils are recruited from the bloodstream by chemotactic factors, such as IL-8, generated and released locally in injured tissues that may also generate NO and superoxide.…”

Section: Discussionmentioning

confidence: 99%

Reactive Nitrogen and Oxygen Species Attenuate Interleukin- 8-induced Neutrophil Chemotactic Activity in Vitro

Sato¹,

Simpson²,

Grisham³

et al. 2000

Journal of Biological Chemistry

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Interleukin-8 (IL-8),1 an 8400-dalton protein, is synthesized and secreted by monocytes, macrophages, and other cells, including epithelial and endothelial cells, lymphocytes, fibroblasts, and keratinocytes (1-3). Current concepts suggest an important role for IL-8 in the pathogenesis of neutrophil-mediated inflammation because of the potent neutrophil chemotactic activity (NCA) of IL-8 and its detection in affected tissues or body fluids taken from patients suffering from neutrophilic inflammatory lesions (3).Peroxynitrite is produced by the rapid reaction of nitric oxide (NO) and superoxide (4, 5). In addition to its role in oxidative reactions, peroxynitrite also nitrates free or protein-associated tyrosine to form the stable product nitrotyrosine by addition of a nitro group to the 3-position adjacent to the hydroxyl group of tyrosine (6). Several studies have shown that peroxynitriteinduced protein nitration may compromise protein function. For example, nitration of tyrosine residues on human IgG abrogates C1q binding (7) and inhibits protein phosphorylation by tyrosine kinase (8).Recently, the tyrosine residue at position 13 of IL-8 has been shown to be important in neutrophil chemotaxis (9). We hypothesized peroxynitrite might regulate NCA by nitrating tyrosine residues. To test this hypothesis, the chemotactic responses of human neutrophils to IL-8 incubated with peroxynitrite and other compounds were evaluated in vitro. We found that peroxynitrite and 3-morpholinosydnonimine (SIN-1), a donor of peroxynitrite, significantly attenuated IL-8-induced NCA. In contrast activated serum and LTB 4 -induced NCA was not inhibited by peroxynitrite significantly. These data suggest that peroxynitrite plays an important role in regulating NCA during inflammation. EXPERIMENTAL PROCEDURESMeasurement of NCA-Human polymorphonuclear leukocytes were isolated from venous blood as described previously (10, 11). Briefly, 15 ml of venous blood was obtained from healthy volunteers and then sedimented with 3% dextran in isotonic saline for 45 min to separate white blood cells from red blood cells. The leukocyte-rich upper layer was collected, and neutrophils were separated from mononuclear cells by Ficoll-Paque density centrifugation (Histopaque 1077, Sigma). Contaminating red blood cells were removed by hypotonic lysis (0.1% KHCO 3 and 0.83% NH 4 Cl). The suspension was then centrifuged at 400 ϫ g for 5 min and washed three times in HBSS (Biofluids, Rockville, MD). The resulting cell pellet, as determined by trypan blue and erythrosin exclusion, consisted of Ͼ96% neutrophils and Ͼ98% viable cells. The cells were suspended in Gey's balanced salt solution (Life Technologies, Inc.) containing 2% bovine serum albumin (Sigma) at a final concentration of 3 ϫ 10 6 cells/ml. NCA was assayed in 48-well microchemotaxis chambers (Neuroprobe, Inc., Cabin John, MD) as described previously (11). The bottom wells of the chamber were filled with 25 l of the chemotactic stimulus or media in duplicate. A 10-m thick polyvinylpyrrolidone-free poly...

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“…Granulocytes labelled with '"In have been observed to move in large numbers (approaching 50% of labelled cells in severe disease) to those parts of the lung affected by bronchiectasis and to move through the bronchial wall exitting the body via the sputum [14]. The destruc tion of elastin in the bronchial tree seen in patients with bronchiectasis would be compatible with release of elastase by such neutrophils and, in view of the intense cell traffic, each individual neutrophil would only need to release a very small quantity of elastin while moving through the bron chial wall for this to cause extensive dam age.…”

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confidence: 99%

Host-Microbe Relationships in Chronic Respiratory Infection

Cole

1989

Respiration

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Infection of the upper and lower respiratory tracts accounts for 85% of the respiratory disease seen by primary-care physicians. Acute infection is usually attributable to microbial virulence but may occur on a background of immune deficiency. Recurrent acute bronchial and pneumonic infection is associated with considerable immunological abnormality (up to 75%) for which a high index of suspicion must be maintained. Chronic bronchial sepsis, on the other hand, has a paradoxically low prevalence of immune deficiency ( < 10%) and the pathogenesis depends on initially compromised mucociliary clearance (by exogenous agents or underlying genetic disease) allowing certain microbes to be selected for airway colonisation according to their ability to release cilio-inhibitory factors and factors damaging ciliated epithelium. Once microbial colonisation is established, the host responds exuberantly with non-specific and immune inflammatory responses which fail to clear the microbial flora but damage the ‘innocent bystander’ lung. This further compromises bronchial clearance mechanisms in a ‘vicious circle’ of events whose end result is progressive lung damage and cardio-respiratory failure.

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Indium-111-Labelled Granulocyte Accumulation in Respiratory Tract of Patients With Bronchiectasis

Cited by 59 publications

References 19 publications

Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Reactive Nitrogen and Oxygen Species Attenuate Interleukin- 8-induced Neutrophil Chemotactic Activity in Vitro

Host-Microbe Relationships in Chronic Respiratory Infection

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Indium-111-Labelled Granulocyte Accumulation in Respiratory Tract of Patients With Bronchiectasis

Cited by 59 publications

References 19 publications

Uptake of18fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Uptake of18fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Reactive Nitrogen and Oxygen Species Attenuate Interleukin- 8-induced Neutrophil Chemotactic Activity in Vitro

Host-Microbe Relationships in Chronic Respiratory Infection

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Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?