Erythropoietin Receptor Is Expressed on Human Peripheral Blood T and B Lymphocytes and Monocytes and Is Modulated by Recombinant Human Erythropoietin Treatment

Abstract

Erythropoietin receptor (EPO-R) appears on the cell surface in the early stages of erythropoiesis. It has also been found on endothelial cells and polymorphonuclear leukocytes, suggesting erythropoietin (EPO) role beyond erythropoiesis itself. Earlier reports have shown that treatment with recombinant human erythropoietin (rhEPO) in chronic renal failure (CRF) patients improves interleukin-2 production and restores the T lymphocyte function. We decided to investigate possible expression of EPO-R on circulating peripheral blood lymphocytes and monocytes of CRF patients in order to assess the possibility of rhEPO direct action on these cells. Flow cytometry was used for detection and quantification of EPO-R, and reverse transcription polymerase chain reaction for detection of the EPO receptor mRNA. Our results show for the first time the existence of EPO-R on cell surface of human T and B lymphocytes and monocytes as well as at the transcriptional activity of the EPO-R gene in these cells, both in healthy and CRF individuals. We have also found significant differences between the numbers of EPO-R molecules on T and B lymphocytes of CRF patients not treated and treated with rhEPO and healthy control. Discovery of EPO-R expression on human lymphocytes suggests that EPO is probably able to directly modulate some signaling pathways important for these cells.

Immunosuppressive Effects of Erythropoietin on Human Alloreactive T Cells

“…Our results extend previously published work by others documenting EPO-R on human T cells 20,21 by uniquely revealing that EPO exhibits immunosuppressive properties. EPO inhibits T-cell proliferation, expansion, and IFN-g production without inducing T-cell death or altering Treg generation (Figures 1-3).…”

Erythropoietin receptor is detectable on peripheral blood lymphocytes and its expression increases in activated T lymphocytes

“…6 Moreover, this year we have also published an article that for the first time describes presence of erythropoietin receptor (EPO-R) on human blood lymphocyte and monocyte surface using quantitative flow cytometry to calculate the exact numbers of these receptors. 7 The notion of EPO-R being expressed by human lymphocytes was supported by our finding of EPO-R mRNA in peripheral blood mononuclear cells as well as in isolated CD4 + T lymphocytes. The results suggested that rhEPO action on those cells can be direct.…”

“…A detailed analysis of EPO-R molecules per one cell is described in our article. 7 We would like to emphasize once more that our studies from over the last 12 years demonstrated that erythropoietin is probably able to modulate or amplify some signaling pathways important for human lymphocyte and monocyte functions. There are also many studies, including ours, demonstrating the role of rhEPO in improving immune responses in CRF patients and at the same time suggesting that EPO/rhEPO may act as an immunomodulatory cytokine in the human organism.…”

“…h of stimulation. 7 Representative histograms are presented in Figure 1. A detailed analysis of EPO-R molecules per one cell is described in our article.…”

The Role of Erythropoietin and its Receptor in the Immune, Central Nervous and Cardiovascular Systems

“…Since the introduction of the drug, many articles describing other, beyond correction of anemia, positive effects of rhEPO therapy have been published. This was related to, among other things, the discovery of receptor expression in cells other than erythroid progenitors, including polymorphonuclear leukocytes (PMNLs) [17] , monocytes and lymphocytes [18] , endothelial cells [19,20] , neurons [21,22] and some tumors cells [23] . Multiple studies suggest that rhEPO/EPO can protect brain tissue from hypoxic damage or prevent ischemia-reperfusion myocardial injury, stimulate angiogenesis and modulate immune responses.…”