Introduction: Cardiovascular disease, eg. atherosclerosis, is the leading cause of death globally. Macrophages role in the formation and progression of atherosclerotic plaques is well established. These highly plastic cells are able to shift their phenotypes and functions according to their environment. Distinct macrophage phenotypes within atherosclerotic plaques have been described with M1 and M2 macrophages being most studied. Different phenotypes can have different functional characteristics and their contributions towards lesion development are not well understood. The aim of our study is to characterise five different macrophage phenotypes, namely M1, M2a, M2c, Mox and M4 for their ability to metabolise lipids and the propensity to form foam cells.
Methods: Human blood derived macrophages were polarised to M1, M2a, M2c, Mox and M4. Lipid uptake was tested by FACS using 488-labelled AcLDL. Foam cells formation was induced with 25μg/ml AcLDL and stained with Oil red O. Enumeration of foam cells were performed by bright-field microscopy.
Results: We observed that M1 and M4 macrophages uptake of AcLDL were lower than M2a, M2c and Mox phenotypes. The amount of AcLDL uptake correlated with the surface expression of CD36, the receptor involved in lipoprotein binding and uptake on the various phenotypes. Similar to their AcLDL uptake profile, the ability to form foam cells is lowest in M1 and highest in M2a and M2c macrophages. Interestingly, Mox macrophages did not readily form foam cells despite their ability to uptake high amount of AcLDL.
Conclusion: Distinct polarised macrophage phenotypes exhibit significant differences in AcLDL uptake, which do not entirely correlate with their ability to form foam cells. This may be attributed to differences in lipid accumulation and cholesterol efflux that is currently under investigation.