Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of group III phospholipase A2 deficiency in mast cells on fibroblast-directed maturation of mast cells in vitro

ABSTRACT: Microenvironment-based alterations in mast cell phenotypes influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast cell maturation via PGD2 receptor (DP1). Mice lacking PLA2G3, L-PGDS or DP1, mast cell-deficient mice reconstituted with PLA2G3- or DP1-null mast cells, or mast cells cocultured with L-PGDS-ablated fibroblasts exhibited impaired mast cell maturation and anaphylaxis. Thus, we describe a lipid-driven PLA2G3-L-PGDS-DP1 loop that drives mast cell maturation.

ORGANISM(S): Mus musculus

PROVIDER: GSE44980 | GEO | 2013/03/09

SECONDARY ACCESSION(S): PRJNA192684

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Mast Cell Maturation is Driven via a Novel Group III Phospholipase A2-Prostaglandin D2-DP1 Receptor Paracrine Axis

Project description:Microenvironment-based alterations in mast cell phenotypes influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast cell maturation via PGD2 receptor (DP1). Mice lacking PLA2G3, L-PGDS or DP1, mast cell-deficient mice reconstituted with PLA2G3- or DP1-null mast cells, or mast cells cocultured with L-PGDS-ablated fibroblasts exhibited impaired mast cell maturation and anaphylaxis. Thus, we describe a lipid-driven PLA2G3-L-PGDS-DP1 loop that drives mast cell maturation. Mast cell maturation; immature and mature bone marrow-derived mast cells (BMMCs); Four-condition experiment (mature BMMCs vs immature BMMCs, Pla2g3M-bM-^@M-^S/M-bM-^@M-^S vs Pla2g3+/+); 3 replicates of Pla2g3+/+ BMMCs, 4 replicates of Pla2g3M-bM-^@M-^S/M-bM-^@M-^S BMMCs, 4 replicates of Pla2g3+/+ cocultured BMMCs, 3 replicates of Pla2g3M-bM-^@M-^S/M-bM-^@M-^S cocultured BMMCs

2013-03-09 | E-GEOD-44980 | biostudies-arrayexpress

Lipid-orchestrated paracrine circuit coordinates mast cell maturation through functional interaction with fibroblasts [mast cell]

Project description:Interaction of mast cells (MCs) with fibroblasts is essential for MC maturation within tissue microenvironments, although the underlying mechanism is incompletely understood. Through a phenotypic screening of >30 mouse lines deficient in lipid-related genes, we found that deletion of the lysophosphatidic acid (LPA) receptor LPA1, like that of the phospholipase PLA2G3, the prostaglandin D2 (PGD2) synthase L-PGDS, or the PGD2 receptor DP1, impairs MC maturation and thereby anaphylaxis. Mechanistically, MC-secreted PLA2G3 acts on extracellular vesicles (EVs) to supply lysophospholipids, which are converted by fibroblast-derived autotaxin (ATX) to LPA. Fibroblast LPA1 then integrates multiple pathways required for MC maturation by facilitating integrin-mediated MC-fibroblast adhesion, IL-33-ST2 signaling, L-PGDS-driven PGD2 generation, and feedforward ATX-LPA1 amplification. Defective MC maturation resulting from PLA2G3 deficiency is restored by supplementation with LPA1 agonists or PLA2G3-modified EVs. Thus, the lipid-orchestrated paracrine circuit involving PLA2G3-driven lysophospholipid, eicosanoid, integrin, and cytokine signaling fine-tunes MC-fibroblast communication, ensuring MC maturation.

2024-11-12 | GSE253356 | GEO

Lipid-orchestrated paracrine circuit coordinates mast cell maturation through functional interaction with fibroblasts [fibroblast]

2024-11-12 | GSE253361 | GEO

Lipid-orchestrated paracrine circuit coordinates mast cell maturation and anaphylaxis through functional interaction with fibroblasts [skin scRNA-seq]

2024-11-12 | GSE262558 | GEO

Stem cell factor programs the mast cell activation phenotype

Project description:Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders. Mouse bone marrow-derived mast cells were treated with IL3, IL3+IL33, or IL3+SCF. Six replicates each.

2012-05-01 | E-GEOD-35332 | biostudies-arrayexpress

Mast cells trap and cannibalize swarming neutrophils for metabolic independence

Project description:Neutrophils are activated and attracted to sites of anaphylaxis by degranulating tissue resident mast cells. After they facilitate inflammation and an anti-microbial immune response. However, the dynamics of neutrophils and direct interactions with mast cells are poorly investigated yet. By approaching 2-photon intravital microscopy and live cell imaging, we show that degranulating mast cells induce neutrophil swarming by releasing leukotriene B4 (LTB4). Attracted neutrophils interact with mast cells and surprisingly penetrate inside mast cells where they are stably trapped inside mast cell granules. We call this novel form of cell-in-cell structure “Mast Cell Intracellular Trap” (MIT). Trapped neutrophils and mast cells are both viable in the first 12 hours after MIT formation. However, neutrophils start to dye after 12hrs and translatome analysis of mast cells revealed improved mast cell metabolism and recovery. Therefore, neutrophils allow a faster and more efficient mast cell re-stimulation. Furthermore, mast cells get more resistant to extracellular nutrient limitations. Thus, beside their inflammatory role in anaphylaxis, neutrophils support mast cell recovery by forming a cell in cell structure. This might affect chronic inflammation and recurrent infections.

2024-06-07 | GSE168801 | GEO

MAZR and mast cells

Project description:Mast cells are known to be the key players in type I hypersensitivity reactions in humans and mice. They are critically involved in the development of allergic rhinitis, allergic asthma and systemic anaphylaxis. In this study we investigated the role of the transcriptional regulator MAZR in mast cells by comparing the expression profile of mast cells generated from wild-type (MazrF/F) and MAZR-deficient (MazrF/F x Vav-iCre) bone marrow cells. Our results from the array data demonstrate that MAZR acts preferentially as a transcriptional repressor in mast cells.

2013-10-18 | E-MTAB-1816 | biostudies-arrayexpress

Stem cell factor programs the mast cell activation phenotype

2012-05-02 | GSE35332 | GEO

Transcription profiling of mouse mast cells treated with an antagonist for recepter CRTH2, compound A alone and with CRTH2 ligands, antigen, BW868c and dexatheasone

Project description:These samples are part of a study in which we demonstrate that mast cells express the receptor CRTH2, which is the target for our antagonist compound compound A. We want to examine whether there are differences in RNA expression when the mast cells are treated with the ligands of CRTH2 - PGD2 and DK-PGD2 - compared to no treatment. Also, we want to see if pretreating the cells with compound A can block or change differences in RNA expression induced by either DK-PGD2 or PGD2. The study also looks at Ige loaded cells exposed to antigen and dexamethasone, and cells treated with BW868c - a a highly selective DP receptor antagonist.

2010-06-25 | E-TABM-498 | biostudies-arrayexpress

Expression data of Brain CD11b+ cells from WT and DP1I knockout mice

Project description:PGD2 is the most abundant prostaglandin in the brain. PGD2/DP1 signaling thus has a mulitple roles in regulating the CNS immune response.

2016-07-22 | GSE84653 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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