[Current knowledge of the mechanism of neutrophil granulocyte and macrophage activation for the formation of superoxide anions and of H2O2 and for the causes of defects in the NADPH-oxidase enzyme system involved].
By the binding of activators (f.e. complement factor C5a, leukotriene B4) to receptors of neutrophil granulocytes an activation of a GTP-binding protein is induced, that increases the activity of the phospholipase C in the membrane and thereby the liberation of inositol-1,4,5-phosphate (IP) and of diacylglycerol (DG). The IP effects the liberation of Ca from intracellular stores and an increase in the concentration of Ca-ions in the cytosol. The DG induces an activation of the phosphokinase C near the membrane, that phosphorylates a cytosolic protein, which takes part in the formation of the NADPH-oxidase. The mentioned reactions induce in the membrane the construction of the NADPH-oxidase from a NADPH-binding protein, a flavoprotein, a cytochrome b 558 and from 4 cytosolic proteins. When phagolysosomes are formed, the NADPH-oxidase is part of the membrane, so bactericidal superoxide-anions can be introduced in these. In the chronic granulomatous disease defects in the formation of cytochrome b or of 2 cytosolic proteins exist.
Kolb
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Veterinär-Physiologisch-Chemisches Institut, Veterinärmedizinischen Fakultät, Universität, Leipzig.
D000838:Anions; D002462:Cell Membrane / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D008262:Macrophage Activation / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D000838:Anions; D013481:Superoxides; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins
Neuere Erkenntnisse zum Mechanismus der Aktivierung von neutrophilen Granulozyten und Makrophagen zur Bildung von Superoxid-Anionen und von H2O2 sowie zu den Ursachen von Defekten in dem beteiligten Enzymsystem der NADPH-Oxidase.