Leukocytic function in hypogammaglobulinemia

Mickenberg, Ira D.; Root, Richard K.; Wolff, Sheldon M.

doi:10.1172/jci106370

Cited by 55 publications

(18 citation statements)

References 15 publications

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“…It is not surprising, therefore, that the initial rate of phagocytosis determines the degree to which the rate of glucose oxidation is stimulated. Thus the rate of glucose oxidation is a valid although indirect index of phagocytic rate and has been used for this purpose (16). This relationship is emphasized in the context of studies by others with pharmacologic agents used in attempts to alter specifically metabolic aspects of phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…The granulocyte-erythrocyte fraction was separated from the monocytes and "lymphocytes" by gradient centrifugation on Ficoll-sodium diatrizoate (7). Erythrocytes were removed from the granulocytes by dextran sedimentation and lysis with 0.2% NaCl (9). The monocytes were concentrated by allowing the cells to adhere to plastic (150-cm2 petri dishes-Falcon Plastics, Division of B-D Laboratories, Inc., Los Angeles, Calif.) for 2 h at 370C in minimal essential medium containing Hanks' buffer solution and 15% fetal calf serum (Grand Island Biological Co., Grand Island, N.…”

Section: Methodsmentioning

confidence: 99%

Lipid Peroxidation by Human Blood Phagocytes

Stossel¹,

Mason²,

Smith³

1974

J. Clin. Invest.

161

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“…Aseptic lavage was executed using a 1.1 mm (20 gauge) Angiocath (Parke, Davis and Co., Sandy, UT) for tracheal cannulation and was secured with a ligature (20). Each mouse received 3-5 1.0-ml lavages with modified Hanks balanced salt solution (HBSS) (21). Any lavage fluid contaminated with blood was discarded.…”

Section: Introductionmentioning

confidence: 99%

Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus.

Waldorf¹,

Ruderman²,

Diamond³

1984

J. Clin. Invest.

198

149

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Abstract. To assess the influence of diabetes mellitus in predisposing to pulmonary mucormycosis, a murine model of streptozotocin-induced diabetes was used. Intranasal inoculation of Rhizopus oryzae into diabetic mice resulted in mucormycotic infection with histopathology resembling pulmonary mucormycosis observed in humans. There was no mortality nor infection in inoculated normal mice. Diabetic mice had fatal infections caused by R. oryzae but significantly reduced mortality following inoculation with Aspergillus fumigatus. These findings reflect the specific enhanced susceptibility to mucormycosis observed in human diabetics.Normal bronchoalveolar macrophages formed part of an efficient defense against R. oryzae by inhibiting germination, the critical step in the conversion of R. oryzae to its tissue invasive phase. Bronchoalveolar macrophages inhibited spore germination in vitro and appeared to help prevent germination in vivo. In contrast, spore germination occurred in diabetic mice following intranasal inoculation. Diabetic bronchoalveolar macrophages had a decreased ability to attach to hyphae. In diabetic mice, bronchoalveolar macrophages could damage spores or hyphae of R. oryzae, but serum factors appeared to both promote spore germination and impair attachment of macrophages to spores. This murine model ofdiabetes mellitus provides an opportunity for evaluation of the relative importance of cell and serum-mediated host factors in the pathogenesis of mucormycosis.Portions of this work were presented at a meeting of the American

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Leukocytic function in hypogammaglobulinemia

Cited by 55 publications

References 15 publications

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

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

Lipid Peroxidation by Human Blood Phagocytes

Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus.

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