This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zysk, G.
Right arrow Articles by Heinz, H.-P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zysk, G.
Right arrow Articles by Heinz, H.-P.

 Previous Article  |  Next Article 

Infection and Immunity, February 2001, p. 845-852, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.845-852.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Pneumolysin Is the Main Inducer of Cytotoxicity to Brain Microvascular Endothelial Cells Caused by Streptococcus pneumoniae

Gregor Zysk,1,* Barbara Katharina Schneider-Wald,1 Jae Hyuk Hwang,1 Levente Bejo,1 Kwang Sik Kim,2 Timothy J. Mitchell,3 Regine Hakenbeck,4 and Hans-Peter Heinz1

Department of Medical Microbiology and Virology, University of Duesseldorf, Duesseldorf,1 and Department of Microbiology, University of Kaiserslautern, Kaiserslautern,4 Germany; Division of Infectious Diseases, Children's Hospital, University of Southern California School of Medicine, Los Angeles, California2; and Division of Infection and Immunity, University of Glasgow, Glasgow, Scotland3

Received 26 May 2000/Returned for modification 6 July 2000/Accepted 20 November 2000

In pneumococcal meningitis it is assumed that bacteria cross the blood-brain barrier (BBB), which consists mainly of cerebral endothelial cells. The effect of Streptococcus pneumoniae on the BBB was investigated with an in vitro BBB model using a human brain microvascular endothelial cell line (HBMEC) and primary cultures of bovine brain microvascular endothelial cells (BBMEC). Within a few hours of incubation with pneumococci, rounding and detachment of the HBMEC were observed, and the transendothelial electrical resistance of the BBMEC monolayer decreased markedly. An S. pneumoniae mutant deficient in pneumolysin did not affect the integrity of the endothelial cell monolayer. Neither cell wall fragments nor isolated pneumococcal cell walls induced changes of endothelial cell morphology. However, purified pneumolysin caused endothelial cell damage comparable to that caused by the viable pneumococci. The cell detachment was dependent on de novo protein synthesis and required the activities of caspase and tyrosine kinases. The results show that pneumolysin is an important component for damaging the BBB and may contribute to the entry of pneumococci into the cerebral compartment and to the development of brain edema in pneumococcal meningitis.

* Corresponding author. Mailing address: Department of Medical Microbiology and Virology, University of Duesseldorf, Geb. 22.21/U1, Universitaetsstrasse 1, D-40225 Duesseldorf, Germany. Phone and fax: 49-211-8112496. E-mail: zysk{at}uni-duesseldorf.de.

Infection and Immunity, February 2001, p. 845-852, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.845-852.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Behling-Kelly, E., McClenahan, D., Kim, K. S., Czuprynski, C. J. (2007). Viable "Haemophilus somnus" Induces Myosin Light-Chain Kinase-Dependent Decrease in Brain Endothelial Cell Monolayer Resistance. Infect. Immun. 75: 4572-4581 [Abstract] [Full Text]  
  • Singh, A. K, Jiang, Y., Gupta, S., Benlhabib, E. (2007). Effects of chronic ethanol drinking on the blood brain barrier and ensuing neuronal toxicity in alcohol-preferring rats subjected to intraperitoneal LPS injection. Alcohol Alcohol 42: 385-399 [Abstract] [Full Text]  
  • Moreland, J. G., Bailey, G. (2006). Neutrophil transendothelial migration in vitro to Streptococcus pneumoniae is pneumolysin dependent. Am. J. Physiol. Lung Cell. Mol. Physiol. 290: L833-L840 [Abstract] [Full Text]  
  • Beurg, M., Hafidi, A., Skinner, L., Cowan, G., Hondarrague, Y., Mitchell, T. J, Dulon, D. (2005). The mechanism of pneumolysin-induced cochlear hair cell death in the rat. J. Physiol. 568: 211-227 [Abstract] [Full Text]  
  • Tenenbaum, T., Bloier, C., Adam, R., Reinscheid, D. J., Schroten, H. (2005). Adherence to and Invasion of Human Brain Microvascular Endothelial Cells Are Promoted by Fibrinogen-Binding Protein FbsA of Streptococcus agalactiae. Infect. Immun. 73: 4404-4409 [Abstract] [Full Text]  
  • Pracht, D., Elm, C., Gerber, J., Bergmann, S., Rohde, M., Seiler, M., Kim, K. S., Jenkinson, H. F., Nau, R., Hammerschmidt, S. (2005). PavA of Streptococcus pneumoniae Modulates Adherence, Invasion, and Meningeal Inflammation. Infect. Immun. 73: 2680-2689 [Abstract] [Full Text]  
  • Schmeck, B., Zahlten, J., Moog, K., van Laak, V., Huber, S., Hocke, A. C., Opitz, B., Hoffmann, E., Kracht, M., Zerrahn, J., Hammerschmidt, S., Rosseau, S., Suttorp, N., Hippenstiel, S. (2004). Streptococcus pneumoniae-induced p38 MAPK-dependent Phosphorylation of RelA at the Interleukin-8 Promotor. J. Biol. Chem. 279: 53241-53247 [Abstract] [Full Text]  
  • Schmeck, B., Gross, R., N'Guessan, P. D., Hocke, A. C., Hammerschmidt, S., Mitchell, T. J., Rosseau, S., Suttorp, N., Hippenstiel, S. (2004). Streptococcus pneumoniae-Induced Caspase 6-Dependent Apoptosis in Lung Epithelium. Infect. Immun. 72: 4940-4947 [Abstract] [Full Text]  
  • Vanier, G., Segura, M., Friedl, P., Lacouture, S., Gottschalk, M. (2004). Invasion of Porcine Brain Microvascular Endothelial Cells by Streptococcus suis Serotype 2. Infect. Immun. 72: 1441-1449 [Abstract] [Full Text]  
  • Ren, B., Szalai, A. J., Thomas, O., Hollingshead, S. K., Briles, D. E. (2003). Both Family 1 and Family 2 PspA Proteins Can Inhibit Complement Deposition and Confer Virulence to a Capsular Serotype 3 Strain of Streptococcus pneumoniae. Infect. Immun. 71: 75-85 [Abstract] [Full Text]  
  • Koedel, U., Angele, B., Rupprecht, T., Wagner, H., Roggenkamp, A., Pfister, H.-W., Kirschning, C. J. (2003). Toll-Like Receptor 2 Participates in Mediation of Immune Response in Experimental Pneumococcal Meningitis. J. Immunol. 170: 438-444 [Abstract] [Full Text]  
  • Wellmer, A., Zysk, G., Gerber, J., Kunst, T., von Mering, M., Bunkowski, S., Eiffert, H., Nau, R. (2002). Decreased Virulence of a Pneumolysin-Deficient Strain of Streptococcus pneumoniae in Murine Meningitis. Infect. Immun. 70: 6504-6508 [Abstract] [Full Text]  
  • Marra, A., Lawson, S., Asundi, J. S., Brigham, D., Hromockyj, A. E. (2002). In vivo characterization of the psa genes from Streptococcus pneumoniae in multiple models of infection. Microbiology 148: 1483-1491 [Abstract] [Full Text]  
  • Nau, R., Eiffert, H. (2002). Modulation of Release of Proinflammatory Bacterial Compounds by Antibacterials: Potential Impact on Course of Inflammation and Outcome in Sepsis and Meningitis. Clin. Microbiol. Rev. 15: 95-110 [Abstract] [Full Text]  
  • Marra, A., Brigham, D. (2001). Streptococcus pneumoniae Causes Experimental Meningitis following Intranasal and Otitis Media Infections via a Nonhematogenous Route. Infect. Immun. 69: 7318-7325 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»