Pertussis toxin transiently affects barrier integrity, organelle organization and transmigration of monocytes in a human brain microvascular endothelial cell barrier model.
Encephalopathies and neurological disorders are sometimes associated with respiratory tract infections caused by Bordetella pertussis. For these complications to occur cerebral barriers have to be compromised. Therefore, the influence of pertussis toxin (PT), a decisive virulence determinant of B. pertussis, on endothelial barrier integrity was investigated. Human brain microvascular endothelial cells cultured on Transwell filter devices were used as model for the blood brain barrier. PT, but not its B-oligomer, induced a reduction of the transendothelial resistance and enhanced the permeability for the protein marker horseradish peroxidase. Moreover, transmigration of human monocytes was also elevated suggesting a PT-associated enhancement of the diapedesis of blood leucocytes. Uptake and trafficking of PT was followed by electron microscopy via clathrin-coated pits and accumulation in lysosomes and microvesicular bodies. The breach in barrier integrity was accompanied by a transient disintegration of Golgi structures. Interestingly, PT-induced effects were only transient and restoration of barrier function was observed after 24 h. In summary, intoxication by PT causes a transient destruction of the cellular organization in human brain-derived endothelial cells resulting in a transient disruption of barrier functions. We suggest that these findings reflect early steps in the development of neurological disorders associated with pertussis disease.
Kügler
Silke
S
Institut für Infektiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Westfälische Wilhelms-Universität/Universitätsklinikum Münster, 48149 Münster, Germany.
Böcker
Kathrin
K
Heusipp
Gerhard
G
Greune
Lilo
L
Kim
Kwang Sik
KS
Schmidt
M Alexander
MA
D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002199:Capillary Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008959:Models, Neurological; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D037342:Pertussis Toxin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D037342:Pertussis Toxin