Macrophage-derived iron-bound lipocalin-2 correlates with renal recovery markers following sepsis-induced kidney damage
- 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 (MΦ) 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’ 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 MΦ 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 MΦ-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.
Author: | Christina MertensORCiDGND, Laura KuchlerGND, Anna Sola, Roser Guiteras, Stephan Grein, Bernhard BrüneORCiD, Andreas von KnethenORCiD, Michaela JungORCiD |
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URN: | urn:nbn:de:hebis:30:3-618596 |
DOI: | https://doi.org/10.3390/ijms21207527 |
ISSN: | 1422-0067 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/33065981 |
Parent Title (English): | International journal of molecular sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2020/10/13 |
Date of first Publication: | 2020/10/13 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2021/07/30 |
Tag: | CLP; iron; lipocalin-2; macrophages; renal tubular epithelial cells |
Volume: | 21 |
Page Number: | 17 |
First Page: | 1 |
Last Page: | 17 |
HeBIS-PPN: | 487211812 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Open-Access-Publikationsfonds: | Medizin |
Licence (German): | Creative Commons - Namensnennung 4.0 |