PMID: 9531489Jun 11, 1998Paper

Inhibition of kinases impairs neutrophil activation and killing of Staphylococcus aureus

The Biochemical Journal
B SchnyderB D Car

Abstract

Intracellular phosphorylations polymorphonuclear neutrophils are mediated by kinases, including mitogen activated-protein (MAP) kinases and phosphatidylinositol 3-kinase. In the present study we demonstrate their effector functions upon both ligation of cell-surface seven-transmembrane-spanning receptors by bacterial peptide formylmethionyl-leucylphenylalanine as well as in the process of destruction of Staphylococcus aureus. To regulate neutrophil MAP kinases p38 and p44/42, specifically, we made use of their specific inhibitors 10 microM SK&F 86002 (for p38) and PD 098059 (for activating kinase of p44/42). SK&F 86002 was a potent inhibitor (by 70%) of induced antimicrobial oxygen-radical generation compared with PD 098059 (by 20%). SK&F 86002 and PD 098059 inhibited mobilization of a dominant neutrophil adhesion molecule, beta2 integrin, from cytoplasmic granules to the plasma membrane by 40 and 10% respectively, and the combination of the two drugs resulted in a 90% effect. The combined effect of both drugs was moderate inhibition of bacterial destruction, despite the fact that neither compound had detectable effect on bactericidal activity if applied individually. Bacterial destruction was also inhibited by wortmannin (0.1 ...Continue Reading

Citations

Feb 22, 2012·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Christos Vouras, Stefanos Dailianis
Oct 30, 2016·Microbes and Infection·Katharine M LodgeAlison M Condliffe
Sep 15, 1999·Toxicologic Pathology·B D Car, R T Robertson
May 12, 2000·Critical Care Medicine·T ObataM B Yaffe
Jun 15, 2018·Tissue Engineering. Part C, Methods·Romina BuchsBruno Schnyder
Jul 16, 2008·Expert Opinion on Therapeutic Targets·Senthil DuraisamyPuneet Chopra
Mar 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chang-Won HongDong-Keun Song
May 20, 2020·Infection and Immunity·Kerstin PohlKenneth C Malcolm
Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·N PerskvistO Stendahl
Mar 26, 2003·Infection and Immunity·Costi D SifriStephen B Calderwood
Jun 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Silvia Schnyder-CandrianBruno Schnyder
Jan 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hamid Zarkesh-EsfahaniRichard J M Ross
Jun 13, 2001·American Journal of Physiology. Cell Physiology·D J ElziC C Silliman
Nov 5, 1999·Clinical and Diagnostic Laboratory Immunology·I DanielsA P Haynes

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