High-density lipoprotein inhibits human M1 macrophage polarization through redistribution of caveolin-1 Academic Article uri icon


  • BACKGROUND AND PURPOSE:Monocyte-derived macrophages are critical in the development of atherosclerosis and can adopt a wide range of functional phenotypes depending on their surrounding milieu. High-density lipoproteins (HDLs) have many cardio-protective properties including potent anti-inflammatory effects. We investigated the effects of HDL on human macrophage phenotype and the mechanisms by which these occur. EXPERIMENTAL APPROACH:Human blood monocytes were differentiated into macrophages in the presence or absence of HDL and were then induced to either an inflammatory macrophage (M1) or anti-inflammatory macrophage (M2) phenotype using LPS and IFN-γ or IL-4, respectively. KEY RESULTS:HDL inhibited the induction of macrophages to an M1-phenotype, as evidenced by a decrease in the expression of M1-specific cell surface markers CD192 and CD64, as well as M1-associated inflammatory genes TNF-α, IL-6 and MCP-1 (CCL2). HDL also inhibited M1 function by reducing the production of ROS. In contrast, HDL had no effect on macrophage induction to the M2-phenotype. Similarly, methyl-β-cyclodextrin, a non-specific cholesterol acceptor also suppressed the induction of M1 suggesting that cholesterol efflux is important in this process. Furthermore, HDL decreased membrane caveolin-1 in M1 macrophages. We confirmed that caveolin-1 is required for HDL to inhibit M1 induction as bone marrow-derived macrophages from caveolin-1 knockout mice continued to polarize into M1-phenotype despite the presence of HDL. Moreover, HDL decreased ERK1/2 and STAT3 phosphorylation in M1 macrophages. CONCLUSIONS AND IMPLICATIONS:We concluded that HDL reduces the induction of macrophages to the inflammatory M1-phenotype via redistribution of caveolin-1, preventing the activation of ERK1/2 and STAT3.


  • Lee, Man KS
  • Moore, Xiao-Lei
  • Fu, Yi
  • Al-Sharea, Annas
  • Dragoljevic, Dragana
  • Fernandez-Rojo, Manuel A
  • Parton, Robert
  • Sviridov, Dmitri
  • Murphy, Andrew J
  • Chin-Dusting, Jaye PF

publication date

  • 2016