TY  - JOUR
A1  - Mertens, Christina
A1  - Kuchler, Laura
A1  - Sola, Anna
A1  - Guiteras, Roser
A1  - Grein, Stephan
T1  - Macrophage-derived iron-bound lipocalin-2 correlates with renal recovery markers following sepsis-induced kidney damage
T2  - International journal of molecular sciences
N2  - 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.
KW  - lipocalin-2
KW  - macrophages
KW  - renal tubular epithelial cells
KW  - iron
KW  - CLP
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/61859
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-618596
SN  - 1422-0067
VL  - 21
SP  - 1
EP  - 17
PB  - MDPI
CY  - Basel
ER  -