title: Streptolysin O-permeabilized granulocytes shed L-selectin concomitantly with ceramide generation via neutral sphingomyelinase.
abstract: Cleavage of membrane-associated L-selectin regulates leukocyte rolling on vascular endothelium at sites of inflammation. We report that rapid and massive shedding of L-selectin occurs from granulocytes attacked by the pore-forming bacterial toxin streptolysin O (SLO). Shedding was not induced by an SLO mutant that retained binding capacity but lacked pore-forming activity. Cells permeabilized with SLO exhibited a 1.5-fold increase in the activity of neutral sphingomyelinase, which was accompanied by increased ceramide formation. L-selectin cleavage was inducible by treatment of cells with bacterial sphingomyelinase, and also through exogenous application of a cell-permeable ceramide analog. Our data identify a novel path to the shedding process and show that activation of neutral sphingomyelinase with the generation of ceramide is an important event underlying enhanced sheddase function in cells permeabilized by a pore-forming toxin.
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz, Germany. makowiec@mail.uni-mainz.de
authors.forename: I
authors.initials: I
authors.lastname: Walev
authors.forename: D
authors.initials: D
authors.lastname: Tappe
authors.forename: E
authors.initials: E
authors.lastname: Gulbins
authors.forename: S
authors.initials: S
authors.lastname: Bhakdi
mesh_terms: D001426:Bacterial Proteins; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002518:Ceramides / Q000096:biosynthesis / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology*; D019041:L-Selectin / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D015290:Second Messenger Systems / Q000187:drug effects; D013108:Sphingomyelin Phosphodiesterase / Q000145:classification / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013301:Streptolysins / Q000494:pharmacology*; D000099157:Sphingosine Kinase
chemical_list: D001426:Bacterial Proteins; D002518:Ceramides; D004151:Dipeptides; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007527:Isoenzymes; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010618:Phenanthrolines; D017853:Phosphotransferases (Alcohol Group Acceptor); D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine; D019311:Staurosporine; D013301:Streptolysins; D000099157:Sphingosine Kinase; C092152:N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide; C025964:streptolysin O; C061800:N,N-dimethylsphingosine; C025205:1,10-phenanthroline