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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 - are EPO targets. We show that,\n                    <jats:italic>in vitro<\/jats:italic>\n                    , 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 \ufeff\ufeff\ufeffelevated\ufeff production of the monocyte chemoattractant CCL2, with corresponding egress of Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    monocytes from the BM. In a model of acute acetaminophen-induced liver injury, EPO administration increased the recruitment of Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    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 Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    monocytes in response to liver injury.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-11082-7","type":"journal-article","created":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T10:23:20Z","timestamp":1504002200000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Erythropoietin enhances Kupffer cell number and activity in the challenged liver"],"prefix":"10.1038","volume":"7","author":[{"given":"Dafna","family":"Gilboa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Haim-Ohana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naamit","family":"Deshet-Unger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Ben-Califa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Hiram-Bab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debby","family":"Reuveni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehud","family":"Zigmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Gassmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yankel","family":"Gabet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Varol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drorit","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,4]]},"reference":[{"key":"11082_CR1","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1152\/japplphysiol.00248.2015","volume":"119","author":"M Gassmann","year":"2015","unstructured":"Gassmann, M. & Muckenthaler, M. 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