THP-1 and human peripheral blood mononuclear cell-derived macrophages differ in their capacity to polarize in vitro

Mol Immunol. 2017 Aug;88:58-68. doi: 10.1016/j.molimm.2017.05.027. Epub 2017 Jun 7.

Abstract

Macrophages (Mφ) undergo activation to pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes in response to pathophysiologic stimuli and dysregulation of the M1-M2 balance is often associated with diseases. Therefore, studying mechanisms of macrophage polarization may reveal new drug targets. Human Mφ polarization is generally studied in primary monocyte-derived Mφ (PBMC Mφ) and THP-1-derived Mφ (THP-1 Mφ). We compared the polarization profile of THP-1 Mφ with that of PBMC Mφ to assess the alternative use of THP-1 for polarization studies. Cellular morphology, the expression profiles of 18 genes and 4 cell surface proteins, and phagocytosis capacity for apoptotic cells and S. aureus bioparticles were compared between these Mφ, activated towards M1, M2a, or M2c subsets by stimulation with LPS/IFNγ, IL-4, or IL-10, respectively, for 6h, 24h and 48h. The Mφ types are unique in morphology and basal expression of polarization marker genes, particularly CCL22, in a pre-polarized state, and were differentially sensitive to polarization stimuli. Generally, M1 markers were instantly induced and gradually decreased, while M2 markers were markedly expressed at a later time. Expression profiles of M1 markers were similar between the polarized Mφ types, but M2a cell surface markers demonstrated an IL-4-dependent upregulation only in PBMC Mφ. Polarized THP-1 Mφ but not PBMC Mφ showed distinctive phagocytic capacity for apoptotic cells and bacterial antigens, respectively. In conclusion, our data suggest that THP-1 may be useful for performing studies involving phagocytosis and M1 polarization, rather than M2 polarization.

Keywords: Cell surface receptor; Gene expression; Human polarization marker; Macrophage; Phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Polarity / immunology*
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-10 / pharmacology
  • Interleukin-4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Phagocytosis / immunology*
  • Staphylococcus aureus / immunology*

Substances

  • Biomarkers
  • Lipopolysaccharides
  • Membrane Proteins
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma