RT Journal Article
SR Electronic
T1 Pneumolysin causes cyotoxicity and ciliary stasis in human respiratory epithelial cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P4939
VO 44
IS Suppl 58
A1 Khodor Hazime
A1 Gwyneth Williams
A1 Peter Andrew
A1 Chris O'Callaghan
A1 Robert Hirst
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P4939.abstract
AB Background: Pneumolysin is the cholesterol dependent pore forming toxin that is released from Streptococcus pneumoniae during respiratory infection. The release of pneumolysin is thought to be a sudden event following activation of the bacterial autolysin enzyme. Here we tested the dose response relationship of acute exposure of pneumolysin on human respiratory epithelial cells grown at an air-liquid interface.Aims: To determine the concentration of pneumolysin required to adversely affect human respiratory ciliary function.Methods: Normal human respiratory epithelial cells were grown to a confluent layer and re-growth of cilia from the basal epithelial cells was stimulated by use of an air-liquid interface culture. Light microscopy and high speed video recordings at 1000x magnification were used to determine cilia function and morphological cytotoxicity.Results: Pneumolysin displayed a dose dependent inhibition of ciliary beat frequency with an IC50 of 43.3± 6.9 HU. The common cytotoxic events that were quantified included ciliary dyskinesia, immotility and cytoplasmic extrusion.Conclusion: Pneumolysin caused dose dependent, rapid ciliary inhibition and cytotoxicity, indicating an important role of this toxin in pneumococcal infection. The comparative toxicity with un-ciliated basal cells will be presented.