The effect of an NADH oxidase inhibitor (hydrocortisone) on polymorphonuclear leukocyte bactericidal activity

Mandell, Gerald L.; Rubin, Walter; Hook, Edward W.

doi:10.1172/jci106355

Cited by 167 publications

(55 citation statements)

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“…Hydrocortisone 21-succinate, in high concentration (2.1 mM) has been reported to depress leukocyte oxygen consumption without affecting ingestion of Staphylococci (22). Particle uptake was quantified in that study by counting particles in cells by light microscopy.…”

Section: Discussionmentioning

confidence: 95%

Quantitative Studies of Phagocytosis by Polymorphonuclear Leukocytes: Use of Emulsions to Measure the Initial Rate of Phagocytosis

Stossel¹,

Mason²,

Hartwig³

et al. 1972

J. Clin. Invest.

218

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A B S T R A C T Polymorphonuclear leukocytes suspended in Krebs-Ringer phosphate medium ingest paraffin oil containing Oil Red 0 emulsified with a variety of substances. Spectrophotometric determination of Oil Red O in the cells after uningested particles have been removed by differential centrifugation provides a quantitative measure of phagocytosis. This system has been used to investigate the effects of several drugs and hormones on the initial rate of phagocytosis and to approach the question of how the surface of a particle influences its acceptability as a substrate for phagocytosis. The rate of uptake of paraffin oil emulsified with bovine albumin was constant for 6 min and was proportional to cell concentration when saturating concentrations of paraffin oil emulsion were used. At lower concentrations of substrate, the initial rate of phagocytosis was directly proportional to paraffin oil concentration. The increment in glucose oxidation associated with phagocytosis varied directly with the initial rate of particle uptake. The rate of ingestion of the albumin emulsion was not altered by serum (2-20%, v/v), glucose (5-20 mM), or omission of potassium from the medium. The rate of phagocytosis was decreased 65% if magnesium was omitted, and was essentially zero in the absence of divalent cations. The initial rate of uptake was inhibited by inhibitors of glycolysis, by Nethylmaleimide (0.05-1 mM), colchicine (0.001-0.1 mM), theophylline (1 and 2 mM), dibutyryl cyclic AMP (1 mM), hydrocortisone (2.1 mM), and ethanol (85 mM). Inhibitors of oxidative phosphorylation and dexamethasone (0.01 mM) were without effect, while insulin (2 mU/ml) slightly stimulated the phagocytic rate. Paraffin oil emulsified with different agents was used to approach the question of how the surface of a particle influences its acceptability as a substrate for phagocytosis. Emulsions prepared with nonionic detergents, methylated proteins, and proteins with a weak net charge at pH 7.4 were poorly ingested. On the other hand emulsions prepared with agents of strong net positive or negative charge were rapidly taken up. The effect of divalent cations on the rate of phagocytosis varied with the nature of the emulsifier, but was not related in any simple, direct fashion to the net surface charge of the particles. However, it has not been conclusively established that charge was the only variable of the emulsion particles employed. INTRODUCTIONPhagocytosis is an integrated series of complex events.Certain as yet unidentified characteristics of the surface of a particle cause it to be bound to the plasma membrane of a polymorphonuclear leukocyte which then internalizes it. As the phagocytic vesicle is formed and moves centripetally, lysosomal granules discharge their contents into it and disappear from the cytoplasm, a process termed degranulation. These processes are accompanied by several alterations in the metabolism of the phagocytic cell which have been termed metabolic concomitants of phagocytosis. One of these is an increase in oxidatio...

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Section: Discussionmentioning

confidence: 95%

Quantitative Studies of Phagocytosis by Polymorphonuclear Leukocytes: Use of Emulsions to Measure the Initial Rate of Phagocytosis

Stossel¹,

Mason²,

Hartwig³

et al. 1972

J. Clin. Invest.

218

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show abstract

“…Several studies have documented the inhibitory effect of corticosteroid compounds on several aspects of PMN function including PMN adherence, phagocytosis, and intracellular killing (23)(24)(25)(26). Previous studies of the corticosteroid effect on PMN motility have been performed in adults.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Betamethasone on Neonatal Neutrophil Chemotaxis

et al. 1987

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“…These observations, however, were based on studies with liver lysosomes, subcellular organelles not usually involved with extrahepatic inflammation. Recent studies using phagocytic cells and bactericidal systems have failed to document stabilization by hydrocortisone of the lysosomes in these cells (4)(5)(6). Although Wright and Malawista (4) found less extracellular release of granular enzymes in 5 X 10' M cortisol, neither altered degranulation nor impaired intracellular digestion by lysosomal hydrolases was detected by Mandell, Rubin, and Hook (5) or by Wiener, Marmary, and Curelaru (6).…”

Section: Introductionmentioning

confidence: 99%