{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:18:37Z","timestamp":1760239117112,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T00:00:00Z","timestamp":1602547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2017.130.2"],"award-info":[{"award-number":["2017.130.2"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>During the course of sepsis in critically ill patients, kidney dysfunction and damage are among the first events of a complex scenario toward multi-organ failure and patient death. Acute kidney injury triggers the release of lipocalin-2 (Lcn-2), which is involved in both renal injury and recovery. Taking into account that Lcn-2 binds and transports iron with high affinity, we aimed at clarifying if Lcn-2 fulfills different biological functions according to its iron-loading status and its cellular source during sepsis-induced kidney failure. We assessed Lcn-2 levels both in serum and in the supernatant of short-term cultured renal macrophages (M\u03a6) as well as renal tubular epithelial cells (TEC) isolated from either Sham-operated or cecal ligation and puncture (CLP)-treated septic mice. Total kidney iron content was analyzed by Perls\u2019 staining, while Lcn-2-bound iron in the supernatants of short-term cultured cells was determined by atomic absorption spectroscopy. Lcn-2 protein in serum was rapidly up-regulated at 6 h after sepsis induction and subsequently increased up to 48 h. Lcn-2-levels in the supernatant of TEC peaked at 24 h and were low at 48 h with no change in its iron-loading. In contrast, in renal M\u03a6 Lcn-2 was low at 24 h, but increased at 48 h, where it mainly appeared in its iron-bound form. Whereas TEC-secreted, iron-free Lcn-2 was associated with renal injury, increased M\u03a6-released iron-bound Lcn-2 was linked to renal recovery. Therefore, we hypothesized that both the cellular source of Lcn-2 as well as its iron-load crucially adds to its biological function during sepsis-induced renal injury.<\/jats:p>","DOI":"10.3390\/ijms21207527","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T21:48:38Z","timestamp":1602625718000},"page":"7527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Macrophage-Derived Iron-Bound Lipocalin-2 Correlates with Renal Recovery Markers Following Sepsis-Induced Kidney Damage"],"prefix":"10.3390","volume":"21","author":[{"given":"Christina","family":"Mertens","sequence":"first","affiliation":[{"name":"Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Kuchler","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sola","sequence":"additional","affiliation":[{"name":"Department of Experimental Nephrology, IDIBELL, 08908 L\u2019Hospitalet del Llobregat, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roser","family":"Guiteras","sequence":"additional","affiliation":[{"name":"Department of Experimental Nephrology, IDIBELL, 08908 L\u2019Hospitalet del Llobregat, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Grein","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8237-2841","authenticated-orcid":false,"given":"Bernhard","family":"Br\u00fcne","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany"},{"name":"Project Group Translational Medicine &amp; Pharmacology TMP, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-0365","authenticated-orcid":false,"given":"Andreas","family":"von Knethen","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany"},{"name":"Project Group Translational Medicine &amp; Pharmacology TMP, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 60590 Frankfurt am Main, Germany"},{"name":"Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-5675","authenticated-orcid":false,"given":"Michaela","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1056\/NEJMoa0802639","article-title":"Intensity of renal support in critically ill patients with acute kidney injury","volume":"359","author":"Palevsky","year":"2008","journal-title":"N. 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