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Infection and Immunity, February 2002, p. 1017-1022, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.2.1017-1022.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Sensitivities of Human Monocytes and Epithelial Cells to Pneumolysin Are Different

Robert A. Hirst,1,2 Hasan Yesilkaya,1 Edwin Clitheroe,1 Andrew Rutman,2 Nichola Dufty,1 Timothy J. Mitchell,3 Christopher O’Callaghan,2 and Peter W. Andrew1*

Department of Microbiology and Immunology,1 Department of Child Health, Leicester Royal Infirmary, University of Leicester, Leicester LE1 5WW,2 Division of Infection and Immunity, University of Glasgow, G12 8OO Glasgow, United Kingdom3

Received 28 August 2001/ Returned for modification 17 October 2001/ Accepted 8 November 2001

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 (pIC50) 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 pIC50 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.

* Corresponding author. Mailing address: University of Leicester, Department of Microbiology and Immunology, University Road, P.O. Box 138, Leicester LE1 9HN, United Kingdom. Phone: (0116) 2522941. Fax: (0116) 2525030. E-mail: pwa@le.ac.uk.

Infection and Immunity, February 2002, p. 1017-1022, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.2.1017-1022.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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