title: Sensitivities of human monocytes and epithelial cells to pneumolysin are different.
abstract: The Streptococcus pneumoniae pore-forming toxin, pneumolysin, is an important virulence factor in pneumococcal pneumonia. The effect of pneumolysin on human lung epithelial and monocyte cell viability was compared. Pneumolysin caused a dose-dependent loss of viability of human lung epithelial (A549 and L132) and monocyte (U937 and THP-1) cell lines. Analysis of the dose-response curves revealed similar log 50% inhibitory concentration (pIC(50)) values for A549, L132, and THP-1 of 0.12+/- 0.1, 0.02+/- 0.04, and 0.12+/- 0.13 hemolytic units (HU), respectively, but U937 cells showed a significantly greater pIC(50) of 0.42+/- 0.12 HU. Differentiation of A549 and L132 with phorbol ester or THP-1 with gamma interferon had no effect on their sensitivity to pneumolysin. However, a significant decrease in the potency of pneumolysin against U937 cells followed gamma interferon treatment. The Hill slopes of the inhibition curves were greater than unity, indicating that pneumolysin may act with positive cooperativity. Analysis of pneumolysin-treated THP-1 cells by electron microscopy revealed membrane lesions of between 100 and 200 nm in diameter.
authors.affiliation: Department of Microbiology and Immunology, Leicester Royal Infirmary, University of Leicester, Leicester LE1 5WW, United Kingdom.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hirst
authors.forename: Hasan
authors.initials: H
authors.lastname: Yesilkaya
authors.forename: Edwin
authors.initials: E
authors.lastname: Clitheroe
authors.forename: Andrew
authors.initials: A
authors.lastname: Rutman
authors.forename: Nichola
authors.initials: N
authors.lastname: Dufty
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mitchell
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Callaghan
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D002454:Cell Differentiation; D002460:Cell Line; D003603:Cytotoxins / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D006462:Hemolytic Plaque Technique; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D012756:Sheep; D013296:Streptococcus pneumoniae; D013301:Streptolysins / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D001426:Bacterial Proteins; D003603:Cytotoxins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D007770:L-Lactate Dehydrogenase