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Thromb Haemost 2016; 115(04): 762-772
DOI: 10.1160/TH15-07-0571
Blood Cells, Inflammation and Infection
Schattauer GmbH

Native LDL promotes differentiation of human monocytes to macrophages with an inflammatory phenotype

Annas Al-Sharea   *
1   Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
,
Man Kit Sam Lee   *
1   Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
,
Xiao-Lei Moore
1   Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
,
Lu Fang
1   Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
,
Dmitri Sviridov
1   Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
,
Jaye Chin-Dusting
1   Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
,
Karen L. Andrews
1   Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
,
Andrew J. Murphy
1   Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
› Author Affiliations Financial support: This work was supported by a Program Grant from the National Health and Medical Research Council (NHMRC) of Australia to JCD and supported in part by the Victorian Government’s OIS Program. AJM was supported by a NHMRC Career Development Fellowship (AAP1085752) and a Future Leader Fellowship (100440) from the National Heart Foundation of Australia.
Further Information

Publication History

Received: 17 July 2015

Accepted after major revision: 13 November 2015

Publication Date:
29 November 2017 (online)

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Summary

Recruitment of monocytes in atherosclerosis is dependent upon increased levels of plasma lipoproteins which accumulate in the blood vessel wall. The extracellular milieu can influence the phenotype of monocyte subsets (classical: CD14++CD16-, intermediate: CD14+CD16+ and non-classical: CD14dimCD16++) and macrophages (M1 or M2) and consequently the initiation, progression and/or regression of atherosclerosis. However, it is not known what effect lipoproteins, in particular native low-density lipoproteins (nLDL), have on the polarisation of monocyte-derived macrophages. Monocytes were differentiated into macrophages in the presence of nLDL. nLDL increased gene expression of the inflammatory cytokines TNFα and IL-6 in macrophages polarised towards the M1 phenotype while decreasing the M2 surface markers, CD206 and CD200R and the anti-inflammatory cytokines TGFβ and IL-10. Compared to the classical and intermediate subsets, the non-classical subset-derived macrophages had a reduced ability to respond to M1 stimuli (LPS and IFNγ). nLDL enhanced the TNFα and IL-6 gene expression in macrophages from all monocyte subsets, indicating an inflammatory effect of nLDL. Further, the classical and intermediate subsets both responded to M2 stimuli (IL-4) with upregulation of TGFβ and SR-B1 mRNA; an effect, which was reduced by nLDL. In contrast, the non-classical subset failed to respond to IL-4 or nLDL, suggesting it may be unable to polarise into M2 macrophages. Our data suggests that monocyte interaction with nLDL significantly affects macrophage polarisation and that this interaction appears to be subset dependent.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Monocyte subsets - macrophages - native LDL - polarisation

* These authors contributed equally.


 

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