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Pneumolysin is the main inducer of cytotoxicity to brain microvascular endothelial cells caused by Streptococcus pneumoniae.
- Source :
-
Infection and immunity [Infect Immun] 2001 Feb; Vol. 69 (2), pp. 845-52. - Publication Year :
- 2001
-
Abstract
- 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.
- Subjects :
- Animals
Anti-Bacterial Agents pharmacology
Bacterial Proteins
Blood-Brain Barrier
Caspases physiology
Cattle
Cell Wall physiology
Endothelium, Vascular pathology
Hot Temperature
Microcirculation drug effects
Phosphorylation
Protein Biosynthesis
Rats
Brain blood supply
Endothelium, Vascular drug effects
Streptococcus pneumoniae pathogenicity
Streptolysins toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0019-9567
- Volume :
- 69
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 11159977
- Full Text :
- https://doi.org/10.1128/IAI.69.2.845-852.2001