Adenosine production inside rat polymorphonuclear leucocytes

Newby, Andrew C.; Holmquist, C A

doi:10.1042/bj2000399

Cited by 59 publications

(44 citation statements)

References 19 publications

(30 reference statements)

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“…This agrees with results from studies using perfused hearts (Frick & Lowenstein, 1976;Schutz et al, 1981) and also with a study by Newby & Holmquist (1981), in which rat polymorphonuclear leukocytes, challenged by 2'-deoxyglucose, were found to produce adenosine at equal rates in the presence and absence of an antibody against the membrane-bound 5'-nucleotidase. All of these studies speak against the required participation of plasma membrane 5'-nucleotidase in the adenosine production of mammalian cells in response to hypoxia or 2-deoxyglucose.…”

Section: Discussionsupporting

confidence: 90%

The mechanism of adenosine release from hypoxic rat liver cells

Belloni

Elkin

Giannotto

1985

British J Pharmacology

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Section: Discussionsupporting

confidence: 90%

The mechanism of adenosine release from hypoxic rat liver cells

Belloni

Elkin

Giannotto

1985

British J Pharmacology

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“…Our results thus indicate that, in contrast to rabbit PMNs (36), but similar to sheep and dog erythrocytes (37), human PMNs may only have a poorly efficient, low capacity nucleoside transport system. That the formation ofadenosine induced by 2-deoxyglucose in rat PMNs proceeded intracellularly and was accompanied by an increase in AMP (38) further indicates that important species differences exist with respect to the metabolic characteristics of PMNs.…”

Section: Nucleoside Transportmentioning

confidence: 93%

Purine catabolism in polymorphonuclear neutrophils. Phorbol myristate acetate-induced accumulation of adenosine owing to inactivation of extracellularly released adenosine deaminase.

Waeg

Berghe²

1991

J. Clin. Invest.

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Since physiological concentrations (0.1-1 pM) of adenosine influence the functions of human polymorphonuclear neutrophils (PMNs), we investigated the metabolism of adenosine in suspensions of stimulated and unstimulated PMNs. Stimulation with phorbol myristate acetate (PMA, 1 MM), but not by zymosan (0.5 mg/ml) or N-formyl-methionyl-leucyl-phenylalanine (fMLP, 1 MM), provoked an accumulation of endogenous adenosine at a rate of 23±1.0 amol/cell per minute. A similar accumulation was observed with both unstimulated and stimulated PMNs after the addition of deoxycoformycin (dCF, 1-100 MM), an inhibitor of adenosine deaminase. Exogenous adenosine (10 MM) was deaminated at a rate of 9.8±3.7 amol/ cell per minute in control or zymosan or fMLP-stimulated PMN suspensions. This deamination was nearly completely suppressed when the PMNs had been stimulated with PMA. In contrast, the activity of adenosine deaminase in PMN lysates (231±72 amol/cell per minute) was not modified by PMA stimulation. a,#-Methyleneadenosine 5'-diphosphate (AMPCP, 2.5 mM), an inhibitor of membranous ecto-5'-nucleotidase, profoundly inhibited endogenous adenosine accumulation under all conditions. PMA stimulation also provoked an inactivation of extracellular adenosine d purine nucleoside phosphorylase, and lactate dehydrogenase in PMN suspensions. We concluded that PMNs, even when not stimulated, continuously produce adenosine by dephosphorylation of extracellularly released adenylates; and that stimulation of PMNs by PMA causes adenosine accumulation owing to the inactivation of adenosine deaminase released by broken cells. (J. Clin. Invest. 1991. 87:305-312.)

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“…It should be noted that Tauber and Roberts, using 31P nuclear magnetic resonance to estimate cellular ATP and ADP concentrations during stimulation with PMA and STZ, demonstrated no increase in ADP concentration despite a significant fall in ATP concentrations (24). Likewise, Newby and Holmquist (32) found that when rat neutrophils were depleted of ATP by incubation with 2-deoxyglucose, the ATP was quantitatively recovered as hypoxanthine through inosine monophosphate. It might be that the irreversible loss of adenine nucleotides observed during phagocytosis is a limiting factor in determining the extent and duration of particle ingestion.…”

Section: Methodsmentioning

confidence: 98%

Energy Metabolism of Human Neutrophils during Phagocytosis

Borregaard¹,

Herlin²

1982

J. Clin. Invest.

424

372

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A B S T R A C T Detailed quantitative studies were performed on the generation and utilization of energy by resting and phagocytosing human neutrophils. The ATP content was 1.9 fmol/cell, was constant during rest, and was not influenced by the presence or absence of glucose in the medium. The intracellular content of phosphocreatine was less than 0.2 fmol/cell.In the presence of glucose, ATP was generated almost exclusively from lactate produced from glucose taken up from the surrounding medium. The amount of lactate produced could account for 85% of the glucose taken up by the cells, and the intracellular glycosyl store, glycogen, was not drawn upon. The rate of ATP generation as calculated from the rate of lactate production was 1.3 fmol/cell/min. During phagocytosis, there was no measurable increase in glucose consumption or lactate production, and the ATP content fell rapidly to 0.8 fmol/cell. This disappearance of ATP was apparently irreversible since no corresponding increase in ADP or AMP was observed. It therefore appears that this phagocytosis-induced fall in ATP concentration represents all the extra energy utilized in human neutrophils in the presence of glucose.In the absence of glucose, the rate of ATP generation in the resting cell was considerably smaller, 0.75 fmol/ cell per min, as calculated from the rate of glycolysis, which is sustained exclusively by glycogenolysis. Under this condition, however, phagocytosis induces significant enhancement of glycogenolysis and the rate of lactate production is increased by 60%, raising the rate of ATP generation to 1.2 fmol/cell per min. Nonetheless, the ATP content drops significantly from 1.9 to 1.0 fmol/cell.Neutrophils from patients with chronic granulomatous disease have the same rate of glycolysis and Address reprint requests to Dr.

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Adenosine production inside rat polymorphonuclear leucocytes

Cited by 59 publications

References 19 publications

The mechanism of adenosine release from hypoxic rat liver cells

The mechanism of adenosine release from hypoxic rat liver cells

Purine catabolism in polymorphonuclear neutrophils. Phorbol myristate acetate-induced accumulation of adenosine owing to inactivation of extracellularly released adenosine deaminase.

Energy Metabolism of Human Neutrophils during Phagocytosis

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