TY - JOUR U1 - Wissenschaftlicher Artikel A1 - Ziesemer, Sabine A1 - Möller, Nils A1 - Nitsch, Andreas A1 - Müller, Christian A1 - Beule, Achim A1 - Hildebrandt, Jan-Peter T1 - Sphingomyelin Depletion from Plasma Membranes of Human Airway Epithelial Cells Completely Abrogates the Deleterious Actions of S. aureus Alpha-Toxin JF - Toxins N2 - Interaction of Staphylococcus aureus alpha-toxin (hemolysin A, Hla) with eukaryotic cell membranes is mediated by proteinaceous receptors and certain lipid domains in host cell plasma membranes. Hla is secreted as a 33 kDa monomer that forms heptameric transmembrane pores whose action compromises maintenance of cell shape and epithelial tightness. It is not exactly known whether certain membrane lipid domains of host cells facilitate adhesion of Ha monomers, oligomerization, or pore formation. We used sphingomyelinase (hemolysin B, Hlb) expressed by some strains of staphylococci to pre-treat airway epithelial model cells in order to specifically decrease the sphingomyelin (SM) abundance in their plasma membranes. Such a pre-incubation exclusively removed SM from the plasma membrane lipid fraction. It abrogated the formation of heptamers and prevented the formation of functional transmembrane pores. Hla exposure of rHlb pre-treated cells did not result in increases in [Ca2+]i, did not induce any microscopically visible changes in cell shape or formation of paracellular gaps, and did not induce hypo-phosphorylation of the actin depolymerizing factor cofilin as usual. Removal of sphingomyelin from the plasma membranes of human airway epithelial cells completely abrogates the deleterious actions of Staphylococcus aureus alpha-toxin. KW - sphingomyelin KW - airway epithelial cells KW - cell physiology KW - Staphylococcus aureus KW - alpha-toxin Y1 - 2019 UN - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-31966 SN - 2072-6651 SS - 2072-6651 U6 - https://doi.org/10.3390/toxins11020126 DO - https://doi.org/10.3390/toxins11020126 VL - 11 IS - 2 SP - 13 S1 - 13 PB - MDPI CY - Basel ER -