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.
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).
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.
Project description:Macrophages are central in regulating iron homeostasis. Transcription repressor Bach2 regulates by heme. Here we investigated the relationship between heme-regulated Bach2 and macrophage in spleen. We found that gene expression were not many change between WT and Bach2 knock out mice in red-pulp macrophage.Our results suggest that the function of the red-pulp macrophage is not dependent on according to expression of Bach2.
Project description:Thiele2013 - Spleen cells in red pulp
The model of spleen cells in red pulp metabolism is derived from the community-driven global reconstruction of human metabolism (version 2.02, MODEL1109130000
).
This model is described in the article:
A community-driven global reconstruction of human metabolism.
Thiele I, et al
.
Nature Biotechnology
Abstract:
Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven,
consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared
with its predecessors, the reconstruction has improved topological and functional features, including ~2x more reactions and ~1.7x more unique metabolites. Using
Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic
data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically
generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will
facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
This model is hosted on BioModels Database
and identified by: MODEL1310110060
.
To cite BioModels Database, please use: BioModels Database: An enhanced,
curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer
to CC0 Public Domain Dedication
for more information.
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.
Project description:Expression data from mouse spleen pre-Red Pulp Macrophages (PreRPM), circulating Ly6C-low subset of monocytes (patrolling monocytes), and bone marrow derived macrophages (BMDM)
Project description: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.
Project description:We have defined a novel population of monocyte-derived hemophagocytes (inflammatory hemophagocytes (iHPC)) found in situations of inflammation, such as TLR7.1 mice that overexpress TLR7. These iHPC are similar yet distinct from red pulp macrophages (RPM) and differentiate in response to chronic TLR7 signals. In vivo, iHPC phagocytose red blood cells and platelets causing anemia and thrombocytopenia. We performed this study to further understand iHPC and their relationship to RPM and monocytes and determine what gene signatures make them unique.