Sequential phospholipase activation in the stimulation of the neutrophil NADPH oxidase.
Stimulation of human neutrophils with the chemotactic peptide fMet-Leu-Phe results in activation of a rapid, transient burst of oxidant secretion, which reaches a maximal rate by about 1 min after stimulation. This phase of oxidant secretion is then followed by intracellular oxidant production, which is detected by luminol chemiluminescence but not by assays such as cytochrome c reduction or scopoletin oxidation. The rapid phase of oxidant secretion requires increases in intracellular free Ca2+ and phospholipase A2 activity, but not the activities of phospholipase D or protein kinase C. In contrast, intracellular oxidant production requires the activities of phospholipase D and protein kinase C. A model is thus proposed suggesting the sequential activation of different phospholipases which activate oxidase molecules on the plasma membrane or else from the membranes of specific granules.
Watson
F
F
Department of Biochemistry, University of Liverpool, UK.
Robinson
J J
JJ
Edwards
S W
SW
D002118:Calcium / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D006801:Humans; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000097:blood*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology*; D010739:Phospholipase D / Q000097:blood*; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D010741:Phospholipases A; D054467:Phospholipases A2; D010739:Phospholipase D; D002118:Calcium