title: Efflux transport of serum amyloid P component at the blood-brain barrier.
abstract: Serum amyloid P component (SAP), a member of the innate immune system, does not penetrate the brain in physiological conditions; however, SAP is a stabilizing component of the amyloid plaques in neurodegenerative diseases. We investigated the cerebrovascular transport of human SAP in animal experiments and in culture blood-brain barrier (BBB) models. After intravenous injection, no SAP could be detected by immunohistochemistry or ELISA in healthy rat brains. Salmonella typhimurium lipopolysaccharide injection increased BBB permeability for SAP and the number of cerebral vessels labeled with fluorescein isothiocyanate (FITC)-SAP in mice. Furthermore, when SAP was injected to the rat hippocampus, a time-dependent decrease in brain concentration was seen demonstrating a rapid SAP efflux transport in vivo. A temperature-dependent bidirectional transport of FITC-SAP was observed in rat brain endothelial monolayers. The permeability coefficient for FITC-SAP was significantly higher in abluminal to luminal (brain to blood) than in the opposite direction. The luminal release of FITC-SAP from loaded endothelial cells was also significantly higher than the abluminal one. Our data indicate the presence of BBB efflux transport mechanisms protecting the brain from SAP penetration. Damaged BBB integrity due to pathological insults may increase brain SAP concentration contributing to development of neurodegenerative diseases.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Veszelka
authors.forename: Judit
authors.initials: J
authors.lastname: Laszy
authors.forename: Tamás
authors.initials: T
authors.lastname: Pázmány
authors.forename: László
authors.initials: L
authors.lastname: Németh
authors.forename: Izabella
authors.initials: I
authors.lastname: Obál
authors.forename: László
authors.initials: L
authors.lastname: Fábián
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.forename: Csongor S
authors.initials: CS
authors.lastname: Abrahám
authors.forename: Mária A
authors.initials: MA
authors.lastname: Deli
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Urbányi
keywords: blood–brain barrier; brain efflux transport; brain endothelial cells; lipopolysaccharide; neurodegenerative diseases; neuroimmunology; permeability; serum amyloid P component