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

Macrophages (Mf) 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 Mf polarization is generally studied in primary monocyte-derived Mf (PBMC Mf) and THP-1-derived Mf (THP-1 Mf). We compared the polarization profile of THP-1 Mf with that of PBMC Mf 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 Mf, activated towards M1, M2a, or M2c subsets by stimulation with LPS/IFNg, IL-4, or IL-10, respectively, for 6 h, 24 h and 48 h. The Mf 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 Mf types, but M2a cell surface markers demonstrated an IL-4-dependent upregulation only in PBMC Mf. Polarized THP-1 Mf but not PBMC Mf 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.