Erythropoietin enhances Kupffer cell number and activity in the challenged liver

Dafna Gilboa, Yasmin Haim-Ohana, Naamit Deshet-Unger, Nathalie Ben-Califa, Sahar Hiram-Bab, Debby Reuveni, Ehud Zigmond, Max Gassmann, Yankel Gabet, Chen Varol, Drorit Neumann*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Erythropoietin (EPO) is the main hormone driving mammalian erythropoiesis, with activity mediated via the surface receptor, EPO-R, on erythroid progenitor cells. Recombinant human EPO is currently used clinically for the treatment of anemia in patients with end-stage renal disease, and in certain cancer patients suffering from anemia induced either by the tumor itself or by chemotherapy. EPO-R expression is also detected in non-erythroid cells, including macrophages present in the peritoneum, spleen, and bone marrow (BM). Here we demonstrate that Kupffer cells (KCs)-the liver-resident macrophages-A re EPO targets. We show that, in vitro, EPO initiated intracellular signalling and enhanced phagocytosis in a rat KC line (RKC-2) and in sorted KCs. Moreover, continuous EPO administration in mice, resulted in an increased number of KCs, up-regulation of liver EPO-R expression and elevated production of the monocyte chemoattractant CCL2, with corresponding egress of Ly6Chi monocytes from the BM. In a model of acute acetaminophen-induced liver injury, EPO administration increased the recruitment of Ly6Chi monocytes and neutrophils to the liver. Taken together, our results reveal a new role for EPO in stimulating KC proliferation and phagocytosis, and in recruiting Ly6Chi monocytes in response to liver injury.

Original languageEnglish
Article number10379
JournalScientific Reports
Issue number1
StatePublished - 1 Dec 2017


Dive into the research topics of 'Erythropoietin enhances Kupffer cell number and activity in the challenged liver'. Together they form a unique fingerprint.

Cite this