Erythropoietin Directly Affects Human Macrophage Functionality

Objective: We studied direct effects of Erythropoietin (Epo) on functional properties of human monocytes/macrophages (Mc/Mphs) in vitro. Methods: Cells expressing CD14 marker were isolated from human peripheral blood mononuclear cells (PBMCs) by positive magnetic separation. Mc/Mphs were cultured without or with bacterial lipopolysaccharide (LPS) in the absence or presence of Epo for 24 h. Results: We showed that Epo treatment hoticeably reduces the percentages of CD14+ cells, CD124 (alpha subunit of IL-4 receptor)+ cells and CD197 (CCR7)+ cells in non-activated Mph cultures without affecting the levels of CD16 (low-affinity Fc-receptor)+ and CD119 (interferon-γ (IFN-γ) receptor)+ cells. Epo also markedly reduced percentages of CD197+ cells in LPS-activated Mc/Mphs, without significantly affecting the expression of all other molecular markers studied. In addition, Epo caused moderate up-regulation of interleukin-1β (IL-1β) and IL-6 production in resting Mc/Mph cultures, as compared to the down-regulation of IL-1β and IL-6 production in LPS-activated cells. No Epomediated effects on tumor necrosis factor-α (TNF-α) and IL-10 production were observed. Conclusion: Our data suggests that Epo effects on Mph functionality are largely dependent on the baseline activation status of these cells, and that Epo exerts no distinct direct effects on the particular Mph polarization pathway. Keywords: Erythropoietin, monocyte/macrophage, lipopolysaccharide, cytokine, immunoregulation, PBMCs.