Phenotypic and functional changes of GM-CSF differentiated human macrophages following exposure to apoptotic neutrophils

Abstract

The engulfment of apoptotic cells by monocytes and unprimed macrophages results in M2 polarization. In the current study, we investigated whether apoptotic cells influence the phenotypic and functional characteristics of GM-CSF-differentiated human macrophages (GM-Mφ). Our results demonstrate that GM-Mφ preincubated with apoptotic neutrophils (GM-Mφ_Neu) show significantly increased expression of CD206 and FasL and decreased capacity to stimulate allogeneic T-cell proliferation thus adopting M2 features. The 27-plex analysis demonstrates the down-regulation of 24 cytokines (including IL-10) in GM-Mφ_Neu cultures. In contrast, apoptotic neutrophils enhance PGE2 synthesis by GM-Mφ, and blocking PGE2 production with indomethacin restores an allostimulatory activity of GM-MφNeu. These data provide evidence that GM-Mφ following exposure to apoptotic cells acquire features of M2 cells. Given the global suppression of cytokine secretion, GM-Mφ_Neu resemble deactivated (M2c) macrophages, and their capacity to inhibit allogeneic T-cell proliferation appears to be mediated by an enhanced synthesis of PGE2 but not IL-10.

Keywords: Allostimulatory activity; Apoptotic neutrophils; Cytokines; Macrophage polarization; PGE2.