title: Degradation of microvascular brain endothelial cell beta-catenin after co-culture with activated neutrophils from patients undergoing cardiac surgery with prolonged cardiopulmonary bypass.
abstract: The adhesion of highly activated neutrophils to cerebral microvascular endothelial cells (MVECs) may contribute to disruption and hyperpermeability of the blood-brain barrier (BBB) after cardiac surgery with prolonged cardiopulmonary bypass (CPB). A correlation between CPB duration and neutrophil-mediated BBB damage has not been investigated on the cellular level yet. Therefore, we studied the effects of neutrophils from cardiac surgery patients with CPB time <80 min (group I; n=8) and >80 min (group II; n=8) on the integrity of cultured porcine MVEC. Ex vivo, neutrophils of group II but not of group I significantly degraded the zonula adherens molecule beta-catenin whereas VE-cadherin and occludin were not modified. The transendothelial electric resistance as a measure for the integrity of the endothelial monolayers was reduced over time in both groups. In conclusion, prolonged CPB time entails neutrophil-mediated decrease in MVEC beta-catenin expression, and thus may be an important trigger for BBB disruption.
authors.affiliation: Klinik für Thorax-, Herz- und thorakale Gefässchirurgie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: Alina Maria
authors.initials: AM
authors.lastname: Schuller
authors.forename: Joachim
authors.initials: J
authors.lastname: Windolf
authors.forename: Roman
authors.initials: R
authors.lastname: Blaheta
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wimmer-Greinecker
authors.forename: Anton
authors.initials: A
authors.lastname: Moritz
authors.forename: Martin
authors.initials: M
authors.lastname: Scholz
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D002315:Cardiopulmonary Bypass; D002417:Cattle; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008833:Microcirculation / Q000378:metabolism* / Q000473:pathology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin