Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hemolysis in the spleen facilitates erythrocyte turnover

ABSTRACT: Red pulp macrophages of the spleen mediate daily turnover of billions of senescent erythrocytes. However, the exact molecules and mechanisms involved in sequestration of senescent erythrocytes, their recognition and ultimately their turnover remain unclear and are currently subject to debate. In this study we provide evidence that the splenic environment is of substantial importance in facilitating erythrocyte turnover through induction of haemolysis. Detailed characterization of human spleen and its red pulp macrophages lead to the identification of a population of erythrocytes devoid of haemoglobin without fully disintegrating, so-called erythrocyte ghosts. By in-vivo imaging and transfusion experiments we established that senescent erythrocytes are subject to haemolysis specifically within the spleen. We show that aged erythrocytes are captured by the extracellular matrix within the red pulp of the spleen and that their retention under low shear conditions is key in driving haemolysis. In contrast to senescent erythrocytes, the erythrocyte ghost shells were found to be prone to recognition and breakdown by red pulp macrophages. As such, these data put forward haemolysis as an efficient mechanism for the turnover of senescent erythrocytes which alters our current understanding on how erythrocyte turnover is regulated.

ORGANISM(S): Homo sapiens

PROVIDER: GSE121629 | GEO | 2020/09/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Heme regulates the development of iron-recycling macrophages from monocytes (sorted splenocytes)

Project description:Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis. Global gene expression pattern of Spic+ monocytes, Spic- monocytes, and Spic high red pulp macrophages were compared by sorting these cells from Spic(igfp/+) splenocytes and performing microarray-based gene expression profiling.

2014-03-14 | GSE46984 | GEO

Heme regulates the development of iron-recycling macrophages from monocytes (sorted splenocytes)

2014-03-14 | E-GEOD-46984 | biostudies-arrayexpress

Tissue printing: splenic red pulp macrophages of once-malaria infected mice are transcriptionally identical to prenatally seeded red pulp macrophages from uninfected mice.

Project description:Acute malaria infection with P. chabaudi obliterates embryonically seeded tissue-resident red pulp macrophages in the spleen of C57Bl/6J mice - regardless of whether the infection is mild (mosquito transmitted P. chabaudi AS - no hyperparasitaemia, no measurable clinical manifestations of disease other than low-grade anaemia) or severe (mosquito transmitted P. chabaudi AJ - acute hyperparasitaemia, severe anaemia, hypothermia and prostration). Red pulp macrophages return 100 days later, once mice cleared parasitaemia. We then flow sorted 10,000 red pulp macrophages (lineage-, autofluorescent, F4/80+, B220-, CD11bint, CD11cint) directly into Trizol, extracted total RNA and analysed their transciptome using the affymetrix mouse exon 1.0 ST array. Red pulp macrophages from mice once infected with mild AS or severe AJ P. chabaudi parasites were compared to uninfected age-matched mice. We uncover that red pulp macrophages isolated from the spleens of once-malaria infected mice are transcriptionally identical to prenatally seeded red pulp macrophages from uninfected mice. The spleen tissue niche thus imprints an identical functional profile onto these cells - regardless of their origin.

2020-11-26 | GSE149894 | GEO

Aging-triggered iron-rich insoluble protein aggregates in the spleen originate chiefly from red pulp macrophages.

Project description:Both iron homeostasis and erythropoiesis are known to be affected by aging. Iron needs in mammals are met primarily by iron recycling from senescent red blood cells (RBCs), a task chiefly accomplished by red pulp macrophages (RPMs) in the spleen. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a possibility that has been unexplored to date. In our project, we identified a formation of undegradable iron- and heme-rich extracellular aggregates in the spleens of 10-11-month-old female mice. To better understand the origin of these aggregates, here, we performed: i) protein identification and intrasample quantification (iBAQ) of proteins of magnetically-isolated red pulp macrophages from spleens of two female 8-weeks-old C57BL/6J (maintained on a standard diet) and ii) label-free quantification of proteins of the splenic protein aggregates formed in the mouse spleen 24 hours after intraperitoneal iron dextran injection, using dextran-injected mice as a control. Two 8-week-old C57BL/6J mice per group were analyzed. This dataset is related to the project PXD032900, which describes quanytitative analysis of proteins in aggregates magnetically isolated from spleen of aged (standard or iron-reduced diet) and young mice (standard diet).

2023-02-02 | PXD038660 | Pride

PPARγ is essential for the development of erythroblastic island macrophages and red pulp macrophages

Project description:Macrophages in the bone marrow erythroblastic island (EIM) and splenic red pulp (RPM) are required for terminal erythropoiesis and removal of aged erythrocytes, respectively. This manuscript shows that EIM and RPM development require both PPARg and Spi-C.

2021-02-04 | GSE166085 | GEO

Towards understandingTissue Mϕ heterogeneity and functions using quantitative proteomics

Project description:Resident macrophages are important for maintaining tissue homeostasis and for defence against infections, but their precise functions in different tissues are not fully elucidated.We have used high resolution quantitative proteomics to investigate the functions of splenic red pulp macrophages and peritoneal cavity macrophages in the steady-state. The validation of several proteins at cellular expression levels by the flow cytometry analysis was consistently in agreement with the proteomics data. Peritoneal macrophages were shown to be enriched in a number of key enzymes and metabolic pathways normally associated with the liver, such as metabolism of fructose, detoxification, nitrogen homeostasis and the urea cycle. Supporting observations in proteomics, we find that PM are able to utilise glutamine and glutamate which are rich in peritoneum for urea generation. In comparison, splenic red pulp macrophages were enriched in proteins important for adaptive immunity such as antigen presenting MHC molecules, in addition to proteins required for erythrocyte homeostasis and iron turnover. We also show that these tissue macrophages may utilise carbon and nitrogen substrates for different metabolic fates to support distinct tissue-specific roles. This study provides a valuable resource for biologists interested in the functions of tissue macrophages.

2020-06-24 | PXD019362 | Pride

Heme-induced inhibition of Bach1derepresses Spic.

Project description:Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis. Bone marrow derived macrophages were generated in vitro by culturing WT and Bach1 knock out bone marrow in the presence of GM-CSF and their global gene expression pattern were compared in the presence or absence of heme at the various indicated time points after treatment. GMP and MPP populations were sorted from fetal liver chimeras and pooled by donor genotype. RNA was isolated using an RNAqueous-Micro Kit (Ambion) and submitted for amplification, labeling and hybridization. Expression values were analyzed after RMA quantile normalization using ArrayStar software (DNASTAR).

2014-03-14 | E-GEOD-53796 | biostudies-arrayexpress

Transcript profiling in splenic red pulp macrophages from SIRPa-KO mice and WT mice

Project description:To compare the splenic macrophages between SIRPα-knockout mice and WT mice, we performed a complete transcript profiling of the splenic red pulp macrophages from SIRPα-KO mice compared to WT mice using mRNA microarray as a discovery platform. SIRPα-KO mice and WT mice were kept under the same condition. Macrophages were isolated from spleen red pulp of SIRPα-KO mice and WT mice. RNA was then isolated from the same number of freshly isolated macrophages.

2016-11-22 | GSE78191 | GEO

Organ-specific tissue-resident macrophages dynamics during blood stage malaria

Project description:Blood-stage malaria initiates both innate and adaptive immune responses, inclusive a strong activation of the mononuclear phagocyte network. Here we show that Plasmodium infection results in a transient loss of embryonically established tissue-resident macrophages in spleen, liver and lungs, much before the peak of parasitemia. During acute blood-stage malaria, fate mapping analysis revealed that inflammatory monocytes contribute to the repopulation of the emptied niches of splenic red pulp macrophages and hepatic Kupffer cells, while lung alveolar macrophages refill their niche mainly through self-renewal. Interestingly, the local microenvironment of spleen and liver can “imprint” the molecular characteristics of fetal-derived macrophages in new immigrants from bone marrow including almost identical gene expression profiles and turnover kinetics.

2018-12-11 | GSE115906 | GEO

Heme regulates the development of iron-recycling macrophages from monocytes (heme-treated BMM)

Project description:Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis. Global gene expression pattern of bone marrow-derived macrophages generated with GM-CSF in vitro and treated with heme were compared to those treated with vehicle at 6 hours, 24 hours, and 72 hours after treatment.

2014-03-14 | GSE46983 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data