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Flow cytometry data from mouse tissues, from the Figure 3E & G. from the study - Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance

ABSTRACT: Flow cytometry data from mouse tissues, from the Figure 3E & G.

ORGANISM(S): Mus musculus (mouse)

SUBMITTER: Tomasz Rygiel

PROVIDER: S-BSST2282 | biostudies-other |

REPOSITORIES: biostudies-other

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Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance

Project description:Hemolysis of senescent erythrocytes occurs in the spleen, resulting in hemoglobin (Hb) release. Several diseases are associated with an increased risk of erythrocyte rupture. Iron recycling from Hb and Hb detoxification have been attributed to the sequestration of Hb-haptoglobin complexes by macrophages, however, other routes of Hb clearance might exist. We identified liver sinusoidal endothelial cells (LSECs) as the major cell type that sequesters Hb. Hb uptake involves macropinocytosis and is independent of haptoglobin and the Hb-haptoglobin receptor CD163. LSECs expressed heme oxygenase 1 and hepcidin-controlled ferroportin and were the most efficient cellular scavengers of Hb at doses below the haptoglobin binding capacity. Erythrocyte transfusion assays demonstrated that while splenic red pulp macrophages are efficient in erytrophagocytosis, liver Kupffer cells and LSECs are primarily involved in the clearance of erythrocyte ghosts and Hb, respectively. Using time-course injections of high doses of Hb in mice, we detected transient hepatic iron retention, early induction of Hmox1 specifically in LSECs, and elevation of ferroportin levels. This was associated with transcriptional activation of LSEC Bmp6, followed by hepcidin-mediated transient hypoferremia. Injection of Hb and iron-citrate elicited distinct transcriptional signatures in LSECs and the early Bmp6 induction was phenocopied by erythrocyte lysis upon phenylhydrazine. Collectively, we propose that LSECs provide a key mechanism for Hb clearance, a function that establishes the spleen-liver axis for physiological iron recycling from Hb and contributes to heme detoxification during hemolysis, coupled with the induction of the BMP6-hepcidin axis that restores homeostasis.

2025-08-01 | GSE240270 | GEO

Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance

Project description:Mild hemolysis of senescent erythrocytes occurs physiologically in the spleen resulting in Hb release, whereas pathologic erythrocyte rupture characterizes several diseases. Iron recycling from Hb and Hb detoxification have been attributed to the sequestration of Hb-haptoglobin complexes by macrophages. However, it remained unclear whether other efficient routes of Hb clearance exist. We identified liver sinusoidal endothelial cells (LSECs) as the primary cells responsible for Hb uptake, a process that involves macropinocytosis and operates independently of the Hb-haptoglobin receptor CD163. To further study the functional adaptation of LSECs for Hb clearance, we performed two label-free proteomic analyses: i) using young BALB/C female mice, we compared the proteomes of the following cell types: LSECs, liver macrophages (Kupffer cells), splenic red pulp macrophages, and endothelial cells from the spleen and the heart (set of 15 samples, 5 sample groups, three replicates; ii) we determined changes of protein levels in LSECs after stressed erythrocyte injection in C57BL/6J female mice (set of 10 samples, 2 sample groups, five replicates). In the former analysis, we found that LSECs show high protein levels of enzymes of the heme-catabolic pathway, ferritins, and macropinocytosis regulators. In the later experiment, we identified Hb subunits as the top-increased proteins in LSECs upon erythrocyte injection in mice.

2025-11-12 | PXD051274 | Pride

Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance

Project description: Not available

| S-SCDT-10_1038-S44319-025-00673-5 | biostudies-other