title: ATP Release from Human Airway Epithelial Cells Exposed to Staphylococcus aureus Alpha-Toxin.
abstract: Airway epithelial cells reduce cytosolic ATP content in response to treatment withS. aureusalpha-toxin (hemolysin A, Hla). This study was undertaken to investigate whether this is due to attenuated ATP generation or to release of ATP from the cytosol and extracellular ATP degradation by ecto-enzymes. Exposure of cells to rHla did result in mitochondrial calcium uptake and a moderate decline in mitochondrial membrane potential, indicating that ATP regeneration may have been attenuated. In addition, ATP may have left the cells through transmembrane pores formed by the toxin or through endogenous release channels (e.g., pannexins) activated by cellular stress imposed on the cells by toxin exposure. Exposure of cells to an alpha-toxin mutant (H35L), which attaches to the host cell membrane but does not form transmembrane pores, did not induce ATP release from the cells. The Hla-mediated ATP-release was completely blocked by IB201, a cyclodextrin-inhibitor of the alpha-toxin pore, but was not at all affected by inhibitors of pannexin channels. These results indicate that, while exposure of cells to rHla may somewhat reduce ATP production and cellular ATP content, a portion of the remaining ATP is released to the extracellular space and degraded by ecto-enzymes. The release of ATP from the cells may occur directly through the transmembrane pores formed by alpha-toxin.
authors.affiliation: Animal Physiology and Biochemistry, Ernst Moritz Arndt-University, Felix Hausdorff-Strasse 1, B.10.06, D-17489 Greifswald, Germany. RominaBaaske@hotmail.de.
authors.forename: Romina
authors.initials: R
authors.lastname: Baaske
authors.affiliation: Animal Physiology and Biochemistry, Ernst Moritz Arndt-University, Felix Hausdorff-Strasse 1, B.10.06, D-17489 Greifswald, Germany. mandy.richter91@t-online.de.
authors.forename: Mandy
authors.initials: M
authors.lastname: Richter
authors.affiliation: Animal Physiology and Biochemistry, Ernst Moritz Arndt-University, Felix Hausdorff-Strasse 1, B.10.06, D-17489 Greifswald, Germany. nils.moeller@uni-greifswald.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Möller
authors.affiliation: Animal Physiology and Biochemistry, Ernst Moritz Arndt-University, Felix Hausdorff-Strasse 1, B.10.06, D-17489 Greifswald, Germany. sabine.ziesemer@uni-greifswald.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ziesemer
authors.affiliation: Animal Physiology and Biochemistry, Ernst Moritz Arndt-University, Felix Hausdorff-Strasse 1, B.10.06, D-17489 Greifswald, Germany. ina.eiffler@uni-greifswald.de.
authors.forename: Ina
authors.initials: I
authors.lastname: Eiffler
authors.affiliation: Animal Physiology and Biochemistry, Ernst Moritz Arndt-University, Felix Hausdorff-Strasse 1, B.10.06, D-17489 Greifswald, Germany. christian.mueller@uni-greifswald.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.affiliation: Animal Physiology and Biochemistry, Ernst Moritz Arndt-University, Felix Hausdorff-Strasse 1, B.10.06, D-17489 Greifswald, Germany. jph@uni-greifswald.de.
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Hildebrandt
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001427:Bacterial Toxins / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006460:Hemolysin Proteins / Q000633:toxicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: ATP efflux; Staphylococcus aureus; airway epithelial cells; alpha-toxin; virulence factor