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Correction of metabolic deficiencies in the leukocytes of patients with chronic granulomatous disease

Robert L. Baehner, +2 more
- 01 May 1970 - 
- Vol. 49, Iss: 5, pp 865-870
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TLDR
Evidence is strengthened that the fundamental metabolic lesion in CGD cells during phagocytosis is indeed deficient production of hydrogen peroxide, probably, as previously shown, due to diminished oxidase for reduced nicotinamide adenine dinucleotide.
Abstract
Polymorphonuclear leukocytes from patients with chronic granulomatous disease (CGD) exhibit metabolic and bactericidal deficiencies that may be the result of inadequate production of H2O2. A hydrogen peroxide-generating system was, therefore, inserted into CGD leukocytes. This was accomplished by allowing the cells to phagocytize latex spherules coated with glucose oxidase. This produced an amelioration in the known metabolic deficiencies of these cells during phagocytosis: (a) intracellular (catalatic) formate oxidation dependent upon hydrogen peroxide production was enhanced fourfold; and (b) hexose monophosphate shunt activity, which other workers have shown to be at least partially dependent upon the availability of H2O2, was markedly stimulated. These data strengthen the evidence that the fundamental metabolic lesion in CGD cells during phagocytosis is indeed deficient production of hydrogen peroxide, probably, as previously shown, due to diminished oxidase for reduced nicotinamide adenine dinucleotide.

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Journal ArticleDOI

Generation of superoxide anion by potato tuber protoplasts during the hypersensitive response to hyphal wall components of Phytophthora infestans and specific inhibition of the reaction by suppressors of hypersensitivity

TL;DR: Results indicate that O 2 − generation and NADPH oxidation occur on the plasma-membrane upon incompatible recognition of host cells leading to hypersensitive cell death and suppression of the NADPH-dependent OZ- generation may be involved in compatible relationships in the potato— P. infestans system.
Journal ArticleDOI

Autooxidation as a basis for altered function by polymorphonuclear leukocytes

TL;DR: The hypothesis that directed movement and phagocytosis by PMN are attenuated by autooxidative damage to the cell membrane by endogenously derived H2O2 is supported and that the administration in vivo of vitamin E may prevent this damage by scavenging H2 O2.
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Infectious morbidity and defects of phagocytic function in end-stage renal disease: a review.

TL;DR: The mechanisms of development and the potential causes that have been held responsible for this aspect of the defective immune function are reviewed and it is concluded that the phagocytic defect in ESRD is multifactorial and that each factor should be managed by specific therapeutic approaches.
Journal ArticleDOI

Complete Deficiency of Leukocyte Glucose-6-Phosphate Dehydrogenase with Defective Bactericidal Activity

TL;DR: Data indicate that a complete absence of leukocyte glucose-6-phosphate dehydrogenase with defective hexose monophosphate shunt activity is associated with low H( 2)O(2) production and inadequate bactericidal activity, and further suggest an important role for NADPH in the production of H(2]O(1) in human granulocytes.
Journal ArticleDOI

The role of superoxide anion and hydrogen peroxide in phagocytosis-associated oxidative metabolic reactions.

TL;DR: These studies indicate that the majority of NBT reduction by leukocytes is due to O2, whereas stimulation of the hexose monophosphate shunt and iodination of ingested particles requires H2O2 generated from the increased reduction of oxygen by phagocytizing leukocyte.
References
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Journal Article

Protein Measurement with the Folin Phenol Reagent

TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
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In Vitro Bactericidal Capacity of Human Polymorphonuclear Leukocytes: Diminished Activity in Chronic Granulomatous Disease of Childhood

TL;DR: The deficiency of bactericidal capacity and the minimal degranulation after active phagocytosis by the PMN of these children with an inherited syndrome suggest that separate metabolic processes are involved in phagocytetosis and in intracellular digestion.
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Quantitative Nitroblue Tetrazolium Test in Chronic Granulomatous Disease

TL;DR: Chronic granulomatous disease is an X-linked defect in the killing of certain bacteria by peripheral blood granulocytes and may be detected with the nitroblue tetrazolium (NBT) test.
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Myeloperoxidase-Halide-Hydrogen Peroxide Antibacterial System

TL;DR: Myeloperoxidase, at high concentrations, exerted an antibacterial effect on L. acidophilus in the absence of added halide, which also was temperature- and catalase-sensitive, and suggests that, under the conditions employed, the antibacterial properties of a weak acid extract of guinea pig leukocytes is due, in part, to its peroxid enzyme content, particularly if a halide is present in the reaction mixture.
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