The neurological manifestations of sleeping sickness in man are attributed to the penetration of the blood–brain barrier (BBB) and invasion of the central nervous system by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. However, how African trypanosomes cross the BBB remains an unresolved issue. We have examined the traversal of African trypanosomes across the human BBB using an in vitro BBB model system constructed of human brain microvascular endothelial cells (BMECs) grown on Costar Transwell™ inserts. Human-infective T. b. gambiense strain IL 1852 was found to cross human BMECs far more readily than the animal-infective Trypanosoma brucei brucei strains 427 and TREU 927. Tsetse fly–infective procyclic trypomastigotes did not cross the human BMECs either alone or when coincubated with bloodstream-form T. b. gambiense. After overnight incubation, the integrity of the human BMEC monolayer measured by transendothelial electrical resistance was maintained on the inserts relative to the controls when the endothelial cells were incubated with T. b. brucei. However, decreases in electrical resistance were observed when the BMEC-coated inserts were incubated with T. b. gambiense. Light and electron microscopy studies revealed that T. b. gambiense initially bind at or near intercellular junctions before crossing the BBB paracellularly. This is the first demonstration of paracellular traversal of African trypanosomes across the BBB. Further studies are required to determine the mechanism of BBB traversal by these parasites at the cellular and molecular level.
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October 2004
FUNCTIONAL MORPHOLOGY|
October 01 2004
AFRICAN TRYPANOSOME INTERACTIONS WITH AN IN VITRO MODEL OF THE HUMAN BLOOD–BRAIN BARRIER
Dennis J. Grab;
Dennis J. Grab
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
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Olga Nikolskaia;
Olga Nikolskaia
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
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Yuri V. Kim;
Yuri V. Kim
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
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John D. Lonsdale-Eccles;
John D. Lonsdale-Eccles
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
* Biochemistry & Molecular Genetics, University of Alabama, Birmingham, Alabama 35294
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Susumu Ito;
Susumu Ito
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
† Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115
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Tatsuru Hara;
Tatsuru Hara
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
‡ Department of Parasitology, Kurume University School of Medicine, Fukuoka 830-0011, Japan
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Toshihide Fukuma;
Toshihide Fukuma
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
‡ Department of Parasitology, Kurume University School of Medicine, Fukuoka 830-0011, Japan
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Elvis Nyarko;
Elvis Nyarko
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
‡ Department of Parasitology, Kurume University School of Medicine, Fukuoka 830-0011, Japan
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Kee Jun Kim;
Kee Jun Kim
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
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Monique F. Stins;
Monique F. Stins
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
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Michael J. Delannoy;
Michael J. Delannoy
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
§ Department of Cell Biology and Anatomy, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287
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Jean Rodgers;
Jean Rodgers
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
∥ University of Glasgow Veterinary School, Glasgow G11 6NU, Scotland, U.K
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Kwang Sik Kim
Kwang Sik Kim
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287. [email protected]
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J Parasitol (2004) 90 (5): 970–979.
Citation
Dennis J. Grab, Olga Nikolskaia, Yuri V. Kim, John D. Lonsdale-Eccles, Susumu Ito, Tatsuru Hara, Toshihide Fukuma, Elvis Nyarko, Kee Jun Kim, Monique F. Stins, Michael J. Delannoy, Jean Rodgers, Kwang Sik Kim; AFRICAN TRYPANOSOME INTERACTIONS WITH AN IN VITRO MODEL OF THE HUMAN BLOOD–BRAIN BARRIER. J Parasitol 1 October 2004; 90 (5): 970–979. doi: https://doi.org/10.1645/GE-287R
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