P175Low-density lipoprotein receptor-related protein 5 is differentially expressed in CD14/CD16 macrophage subpopulations and regulates migration

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Abstract

Background

Previous results from our lab have shown the involvement of a member of the LDL receptor family, low-density lipoprotein receptor-related protein 5 (LRP5), in the macrophage reaction to lipid infiltration in atherosclerosis. LRP5 participates in lipid uptake and macrophage migration, critical steps in atherosclerosis progression. We have recently shown that in human coronary artery plaques only a subpopulation of infiltrated macrophages (stained with HAM56) express LRP5. Macrophages are tissue-differentiated monocytes, mononuclear cells that circulate several days until they extravasate and populate healthy and diseased tissues. At least two principal monocyte subsets have been identified that can be distinguished by the expression of surface markers: CD14 + CD16- and CD14 + CD16 + . These two cell subsets are morphologically and functionally different. CD16 + monocytes are known to participate in atherosclerotic progression by the release inflammatory cytokines, adherence to endothelial cells and induction of cellular migration to the vascular wall.

Objective

The aim of this work was to investigate LRP5 expression and function in the two monocyte subsets.

Methods

Magnetic cell sorting (MACS) with CD16 monoclonal antibodies was used to fractionate human monocytes from healthy individuals yielding highly purified populations of CD16 + and CD16- monocytes. Monocytes were differentiated to macrophages and LRP5 levels were measured, LRP5-gene was Over-expressed or silenced and macrophage migration assays performed.

Results

A significantly higher LRP5-mRNA expression level was observed in CD16 + compared to CD16- macrophages. Furthermore, CD16 + macrophages had higher migration rates than CD16-. over-expressing LRP5 in CD16- macrophages rescued their migration capacity. Also, silencing LRP5 in CD16 + macrophages induced reduction of migration.

Conclusions

Here we show for the first time that CD16 + macrophages have a high expression of LRP5. This increased expression results in an increased macrophage migration, a process involved in the infiltration of inflammatory cells in the atherosclerotic lesion.

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