oxLDL uptake by dendritic cells induces upregulation of scavenger-receptors, maturation and differentiation

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-kappa B)-pathway. Methods and results: oxLDL (10 mu g/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-kappa B-pathway. Inhibition of I kappa B alpha-phosphorylation diminished the oxLDL-induced DC-maturation and -differentiation. Conclusion: 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-kappa B-pathway. These results support the hypothesis that vascular inflammation may be aggravated by oxLDL induced DC-activation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.