Defects in the oxidative killing of microorganisms by phagocytic leukocytes.
One of the most important mechanisms of phagocytic killing of ingested microorganisms by leukocytes is the generation of toxic oxygen products. During phagocytosis, neutrophils, as well as monocytes and macrophages, display a strongly increased cell respiration. Quantitatively the most important product of this reaction is hydrogen peroxide. Superoxide is also generated in large amounts, probably as an intermediate in the formation of hydrogen peroxide. Indications exist that singlet oxygen and hydroxyl radicals are also formed in this process. Some of these oxygen products have microbicidal properties by themselves. The effect of hydrogen peroxide is greatly enhanced by the enzyme myeloperoxidase. Several dysfunctions of this sytem are known. In chronic granulomatous disease the enzyme system that produces superoxide is not operative. Thus, no superoxide or hydrogen peroxide is generated, leading to a severely decreased bacterial killing capacity. The exact molecular defects in the X-linked and the autosomal form are as yet undefined. Two variants are also known: lipochrome histiocytosis, with different clinical and histological manifestations, and a 'triggering defect' where only strongly opsonized particles trigger the respiratory burst. Myeloperoxidase deficiency leads to slightly decreased killing capacity, especially for yeasts. In glucose-6-phosphate dehydrogenase deficiency no oxygen radicals or hydrogen peroxide are produced because no equivalents for oxygen reduction can be generated in the hexose-monophosphate shunt. Deficiencies in the glutathione redox system also result in impaired phagocyte function, probably because the cells have to be protected against their own toxic oxygen products.
D001770:Blood Bactericidal Activity; D005260:Female; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide; D006878:Hydroxides; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010101:Oxygen Consumption; D010587:Phagocytosis; D013481:Superoxides
D006878:Hydroxides; D013481:Superoxides; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D005978:Glutathione