title: Inhibition of oxidative burst and chemotaxis in human phagocytes by Legionella pneumophila zinc metalloprotease.
abstract: Legionella pneumophila produces several extracellular proteins, but their role in the pathogenesis of Legionnaires' disease is unclear. This study examined the effects of the L. pneumophila major secretory protein (Msp), a zinc metalloprotease, on the oxidative burst and chemotaxis of human phagocytes. Polymorphonuclear leucocytes (PMNLs) and adherent monocytes treated with sublethal amounts of Msp protease were stimulated with formyl-leucyl-methionyl-phenylalanine (fMLP) and opsonised zymosan particles (ZAP). A dose-dependent inhibition in superoxide anion production in response to both stimuli was seen, and complete inhibition was achieved in PMNLs and monocytes treated with Msp at concentrations of 1500 and 1000 U/ml, respectively. ZAP-induced chemiluminescence by PMNLs and mononuclear cells and fMLP-induced PMNL nitroblue tetrazolium dye reduction were both significantly inhibited. The chemotactic response of PMNLs to fMLP was inhibited in a dose-dependent manner and substantial inhibition (11% of control) was achieved with Msp 1200 U/ml. These results suggest that the L. pneumophila Msp protease alters human phagocyte functional responses significantly and may contribute to the pathogenesis of Legionnaires' disease.
authors.forename: Naren N
authors.initials: NN
authors.lastname: Sahney
authors.affiliation: Department of Microbiology and Immunology and *Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40292, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Summersgill
authors.affiliation: Department of Microbiology and Immunology and *Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Ramirez
authors.forename: Richard D
authors.initials: RD
authors.lastname: Miller
mesh_terms: D001426:Bacterial Proteins; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016952:Legionella pneumophila / Q000201:enzymology*; D007877:Legionnaires' Disease / Q000209:etiology*; D008163:Luminescent Measurements; D008666:Metalloendopeptidases / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D013481:Superoxides; D009580:Nitroblue Tetrazolium; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa