title: Defective protein kinase C-mediated actions in cystic fibrosis neutrophils.
abstract: Neutrophils from cystic fibrosis (CF) patients have been shown previously to be defective in their response (beta-glucuronidase exocytosis, NADPH oxidase activation) to the chemotactic peptide FMLP. In this work, we attempted to identify the defective step in this response. We showed that stimulated CF and control neutrophils do not differ in the formation of inositol phosphates. On the other hand, direct stimulation of protein kinase C with phorbol myristate acetate (PMA) revealed a subnormal stimulation of beta-glucuronidase exocytosis in CF neutrophils. Furthermore, retroinhibition exerted by PMA-activated protein kinase C on stimulated inositol phosphates or on beta-glucuronidase exocytosis was marginal or absent in CF neutrophils, whereas it was significant in the case of control neutrophils. Our observations suggest that the CFTR gene is expressed in neutrophils and is involved in protein kinase C-mediated actions.
authors.affiliation: Université Libre de Bruxelles, Département de Biologie Moléculaire, Rhode-St-Genèse, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Graff
authors.forename: A
authors.initials: A
authors.lastname: Schram-Doumont
authors.forename: C
authors.initials: C
authors.lastname: Szpirer
mesh_terms: D003550:Cystic Fibrosis / Q000201:enzymology*; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D005089:Exocytosis; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D012969:Sodium Fluoride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004075:Diglycerides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015544:Inositol 1,4,5-Trisphosphate; D012969:Sodium Fluoride; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate