title: Phosphatidic acid and not diacylglycerol generated by phospholipase D is functionally linked to the activation of the NADPH oxidase by FMLP in human neutrophils.
abstract: It is widely accepted that the activation of the NADPH oxidase of phagocytes is linked to the stimulation of protein kinase C by diacylglycerol formed by hydrolysis of phospholipids. The main source would be choline containing phospholipid via phospholipase D and phosphatidate phosphohydrolase. This paper presents a condition where the activation of the respiratory burst by FMLP correlates with the formation of phosphatidic acid, via phospholipase D, and not with that of diacylglycerol. In fact: 1) in neutrophils treated with propranolol, an inhibitor of phosphatidate phosphohydrolase, FMLP plus cytochalasin B induces a respiratory burst associated with a stimulation of phospholipase D, formation of phosphatidic acid and complete inhibition of that of diacylglycerol. 2) The respiratory burst by FMLP plus cytochalasin B lasts a few minutes and may be restimulated by propranolol which induces an accumulation of phosphatidic acid. 3) In neutrophils stimulated by FMLP in the absence of cytochalasin B propranolol causes an accumulation of phosphatidic acid and a marked enhancement of the respiratory burst without formation of diacylglycerol. 4) The inhibition of the formation of phosphatidic acid via phospholipase D by butanol inhibits the respiratory burst by FMLP.
authors.affiliation: Institute of General Pathology, University of Verona, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Grzeskowiak
authors.forename: V
authors.initials: V
authors.lastname: Della Bianca
authors.forename: F
authors.initials: F
authors.lastname: Calzetti
authors.forename: G
authors.initials: G
authors.lastname: Gandini
mesh_terms: D000440:Butanols / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004075:Diglycerides / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D005989:Glycerides / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects; D010712:Phosphatidic Acids / Q000502:physiology*; D010739:Phospholipase D / Q000502:physiology*; D010740:Phospholipases / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology
chemical_list: D000440:Butanols; D004075:Diglycerides; D005989:Glycerides; D010712:Phosphatidic Acids; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011433:Propranolol; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D010740:Phospholipases; D010739:Phospholipase D