Reconstituted high-density lipoprotein modulates activation of human leukocytes

Spirig, Rolf; Schaub, Alexander; Kropf, Alain; Miescher, Sylvia; Spycher, Martin O.; Rieben, Robert (2013). Reconstituted high-density lipoprotein modulates activation of human leukocytes. PLoS ONE, 8(8), e71235. Public Library of Science 10.1371/journal.pone.0071235

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An anti-inflammatory effect of reconstituted High Density Lipoprotein (rHDL) has been demonstrated in atherosclerosis and in sepsis models. An increase of adhesion molecules as well as tissue factor expression on endothelial cells in response to inflammatory or danger signals are attenuated by the treatment with rHDL. Here we show the inhibitory effect of rHDL on the activation of human leukocytes in a whole blood assay as well as on monocyte-derived human dendritic cells (DC). Multiplex analysis of human whole blood showed that phytohaemagglutinin (PHA)-induced secretion of the cytokines IL-1β, IL-1RA, IL-2R, IL-6, IL-7, IL-12(p40), IL-15 and IFN-α was inhibited. Furthermore, an inhibitory effect on the production of the chemokines CCL-2, CCL-4, CCL-5, CXCL-9 and CXCL-10 was observed. Activation of granulocytes and CD14+ monocytes by PHA is inhibited dose-dependently by rHDL shown as decreased up-regulation of ICAM-1 surface expression. In addition, we found a strong inhibitory effect of rHDL on toll-like receptor 2 (TLR2)- and TLR4-mediated maturation of DC. Treatment of DC with rHDL prevented the up-regulation of cell surface molecules CD80, CD83 and CD86 and it inhibited the TLR-driven activation of inflammatory transcription factor NF-κB. These findings suggest that rHDL prevents activation of crucial cellular players of cellular immunity and could therefore be a useful reagent to impede inflammation as well as the link between innate and adaptive immunity.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
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UniBE Contributor:

Spirig, Rolf; Miescher-Granger, Sylvia M. and Rieben, Robert

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Verena de Serra Frazao-Bill

Date Deposited:

31 Mar 2014 10:01

Last Modified:

04 Dec 2014 20:35

Publisher DOI:

10.1371/journal.pone.0071235

PubMed ID:

23967171

BORIS DOI:

10.7892/boris.46036

URI:

https://boris.unibe.ch/id/eprint/46036

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