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

Abstract

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
Volume7
Issue number1
DOIs
StatePublished - 1 Dec 2017

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