title: oxLDL uptake by dendritic cells induces upregulation of scavenger-receptors, maturation and differentiation.
abstract: BACKGROUND
  Several studies have proposed a pathogenic role for oxidized LDL (oxLDL) in atherosclerosis. We tested the hypothesis whether oxLDL modulates dendritic cells (DCs), since these important antigen-presenting cells have been implicated in atherogenesis. We investigated the uptake of oxLDL by DCs, the scavenger-receptors involved and the resulting changes in phenotype and cytokine-spectra. In addition, we analyzed the impact of oxLDL on the nuclear transcription factor-kappa B (NF-kappaB)-pathway.
  
  
  RESULTS
  oxLDL (10microg/ml) increased the expression of the scavenger-receptors CD205 and CD36 and decreased the mannose-receptor expression. The lectin-like oxLDL-receptor (LOX-1)-expression was not affected. The endocytotic capacity of dextran and lucifer-yellow was moderately decreased by oxLDL. Blockage of the scavenger-receptors CD36, LOX-1 and CD205 reduced oxLDL uptake. Furthermore, oxLDL induced DC-maturation and triggered differentiation of DCs in myeloid and plasmacytoid DCs. oxLDL decreased IL-10 secretion and increased IL-6 release. Finally, oxLDL induced an activation of the NF-kappaB-pathway. Inhibition of IkappaBalpha-phosphorylation diminished the oxLDL-induced DC-maturation and -differentiation.
  
  
  CONCLUSIONS
  oxLDL uptake by DCs is mediated by the scavenger-receptors LOX-1, CD36, and CD205. oxLDL induces a proinflammatory cytokine profile in human DCs leading to DC-maturation and -differentiation which can, in part, be explained by an activation of the NF-kappaB-pathway. These results support the hypothesis that vascular inflammation may be aggravated by oxLDL induced DC-activation.
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University, Munich, Germany. tsnickel@web.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Nickel
authors.forename: Daniel
authors.initials: D
authors.lastname: Schmauss
authors.forename: Henner
authors.initials: H
authors.lastname: Hanssen
authors.forename: Zelka
authors.initials: Z
authors.lastname: Sicic
authors.forename: Bjarne
authors.initials: B
authors.lastname: Krebs
authors.forename: Sarika
authors.initials: S
authors.lastname: Jankl
authors.forename: Claudia
authors.initials: C
authors.lastname: Summo
authors.forename: Peter
authors.initials: P
authors.lastname: Fraunberger
authors.forename: Autar K
authors.initials: AK
authors.lastname: Walli
authors.forename: Susanne
authors.initials: S
authors.lastname: Pfeiler
authors.forename: Michael
authors.initials: M
authors.lastname: Weis
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology; D015703:Antigens, CD / Q000096:biosynthesis; D050197:Atherosclerosis; D018955:CD36 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis; D008077:Lipoproteins, LDL / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D022423:Myeloid Cells / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D051116:Receptors, Scavenger / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; D018955:CD36 Antigens; D016207:Cytokines; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D008077:Lipoproteins, LDL; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; C495138:Olr1 protein, mouse; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein