Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SAGE analysis of alveolar macrophages from metastatic lung and untreated lung

ABSTRACT: Macrophages in lungs can be classified into two subpopulations, alveolar macrophages (AMs) and interstitial macrophages (IMs), which reside in the alveolar and interstitial spaces, respectively. Accumulating evidence indicates the involvement of IMs in lung metastasis but the roles of AMs in lung metastasis still remain elusive. An intravenous injection of a mouse hepatocellular carcinoma (HCC) cell line, BNL, caused lung metastasis foci with infiltration of AMs and IMs. Comprehensive determination of arachidonic acid (AA) metabolite levels revealed increases in leukotrienes (LTs) and prostaglandins in lungs in this metastasis model. A 5-lipoxygenase (LOX) inhibitor but not a cyclooxygenase inhibitor reduced the numbers of metastatic foci, particularly those with larger sizes. A major 5-LOX metabolite, LTB4, augmented in vitro cell proliferation of human HCC cell lines as well as BNL cells. Moreover, in this lung metastasis course, AMs exhibited higher expression levels of the 5-LOX and LTB4 than IMs. Consistently, 5-LOX-expressing AMs increased in the lungs of human HCC patients with lung metastasis, compared with those without lung metastasis. Furthermore, intratracheal clodronate liposome injection selectively depleted AMs but not IMs, together with reduced LTB4 content and metastatic foci numbers in this lung metastasis process. Finally, IMs in mouse metastatic foci produced CCL2, thereby recruiting blood-borne, CCR2-expressing AMs into lungs. Thus, AMs can be recruited under the guidance of IM-derived CCL2 into metastatic lungs and can eventually contribute to the progression of lung metastasis by providing a potent AA-derived tumor growth promoting mediator, LTB4.

ORGANISM(S): Mus musculus

PROVIDER: GSE106987 | GEO | 2018/02/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Lectin-like oxidized low-density receptor-1 attenuates pneumonia-induced lung injury

Project description:Identifying host factors that contribute to pneumonia incidence and severity are of utmost importance to guiding the development of more effective therapies. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger receptor known to promote vascular injury and inflammation, but it is unknown whether and how LOX-1 functions in the lung. Here, we provide evidence of substantial accumulation of LOX-1 in the lungs of ARDS patients and in mice with pneumonia. Unlike previously described injurious contributions of LOX-1, we found that LOX-1 is uniquely protective in the pulmonary airspaces, limiting proteinaceous edema and inflammation. We also identified alveolar macrophages and recruited neutrophils as two prominent sites of LOX-1 expression in the lungs, whereby macrophages are capable of further induction during pneumonia and neutrophils exhibit a rapid, but heterogenous elevation of LOX-1 in the infected lung. Blockade of LOX-1 led to dysregulated immune signaling in alveolar macrophages, marked by alterations in activation markers and a concomitant elevation of inflammatory gene networks. However, bone marrow chimeras also suggested a prominent role for neutrophils in LOX-1-mediated lung protection, further supported by LOX-1+ neutrophils exhibiting transcriptional changes consistent with reparative processes. Taken together, this work establishes LOX-1 as a tissue-protective factor in the lungs during pneumonia, possibly mediated by its influence on immune signaling in alveolar macrophages (AMs) and LOX-1+ airspace neutrophils.

2022-12-21 | GSE208233 | GEO

β-Catenin signaling in alveolar macrophages enhances lung metastasis through a TNF-dependent mechanism

Project description:The main cause of malignancy-related mortality is metastasis. While metastatic progression is driven by diverse tumor-intrinsic mechanisms, there is a growing appreciation for the contribution of tumor-extrinsic elements of the tumor microenvironment (TME), especially macrophages. Recruited macrophages infiltrating the TME are correlated with worse outcomes, because they are rendered pro-tumorigenic through defined tumor-driven transcription factor-mediated programs. However, the pathways that govern the dysregulation of tissue-resident macrophages (TRMs) are less well understood. Alveolar macrophages (AMs) are a TRM population with critical roles in both tissue homeostasis and metastasis. Wnt/β-catenin signaling is a hallmark of cancer and has been identified as a pathologic regulator of AMs in infection. We tested the hypothesis that β-catenin expression in AMs enhances metastasis in solid tumor models. Using a novel genetic β-catenin gain-of-function approach, we demonstrated that 1) enhanced β-catenin in AMs heightened lung metastasis; 2) β-catenin activity in AMs drove a dysregulated inflammatory program strongly associated with Tnf expression; and 3) localized TNF blockade abrogated this metastatic outcome. Lastly, CTNNB1 and TNF expression were positively correlated in AMs of lung cancer patients. Overall, our findings revealed a novel Wnt/β-catenin–TNF-α pro-metastatic axis in AMs with potential therapeutic implications against tumors refractory to TNF-α induced necrosis.

2022-12-19 | GSE200508 | GEO

Integrative genomic and epigenomic profiling reveals cell-type specific signaling networks in activated lung mononuclear phagocytes [scRNA-seq]

Project description:The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey the lung. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly understood. Here, systematic evaluation of transcriptomes and open chromatin of alveolar macrophages (AMs), interstitial macrophages (IMs) and lung monocytes from two mouse strains enabled inference of common and cell-specific transcriptional regulators. We provide evidence that these factors drive selection of regulatory landscapes that specify distinct phenotypes of AMs and IMs and entrain qualitatively different responses to TLR4 signaling in vivo. These studies reveal a striking divergence in a fundamental innate immune response pathway in AMs and establish a framework for further understanding macrophage diversity in the lung.

2020-01-20 | GSE136915 | GEO

Integrative genomic and epigenomic profiling reveals cell-type specific signaling networks in activated lung mononuclear phagocytes [RNA-seq]

2020-01-20 | GSE136914 | GEO

Integrative genomic and epigenomic profiling reveals cell-type specific signaling networks in activated lung mononuclear phagocytes [RNA-seq/ATAC-seq]

2020-01-20 | GSE137068 | GEO

Leukocyte Recruitment and iBALT Formation Require Chemokine-Secreting Pf4+ Interstitial Macrophages [scRNA-seq: mSk]

Project description:Pulmonary resident macrophages consist of alveolar macrophages (AMs) and interstitial macrophages (IMs). While much is known about the role of AMs, the function of IMs, which are conserved across multiple organs and species, remains unclear. Using single-cell RNA sequencing (scRNA-seq) after inducing acute lung injury, we identified at least six distinct subtypes of pulmonary IMs, based on the chemokines they express. These subtypes are: IMck1 (Ccl2, Ccl7, Ccl12, a few Cxcl14); IMck2-4 (Ccl3, Ccl4, Ccl5, Cxcl2, Cxcl3); IMck5-7 (Ccl6, Ccl8, Ccl9); IMck8 (Cxcl9, Cxcl10); IMck9 (Cxcl13); and IMck10 (Ccl24). Based on the selective chemokine expression profiles observed, we hypothesized that pulmonary IMs play a critical role in recruiting leukocytes and forming inducible bronchus-associated lymphoid tissue (iBALT) in the lung. First, we examined multiple Cre-expressing mice (Lyve1, Nes, Pdpn, and Pf4) for IM specificity by crossing them with Rosa26EYFP. Only the Pf4Cre mice selectively induced EYFP expression in CD206hiCD64hi IMs, where no other immune cell in the lung expressed EYFP. We then created a CD206hiCD64hi IM-depleting mouse by crossing Pf4Cre with Rosa26DTR and CX3CR1DTR. In a bacterial infection and allergic airway disease, depletion of CD206hiCD64hi IMs resulted in diminished leukocyte recruitment and iBALT formation. Overall, our study highlights the increased granularity in IM populations and demonstrates a division of labor for cellular recruitment and iBALT formation in the lung. Furthermore, the study suggests that the specific combination of chemokines expressed by IMs are tightly regulated, like Th cytokine-producing cells.

2023-03-03 | GSE225666 | GEO

Leukocyte Recruitment and iBALT Formation Require Chemokine-Secreting Pf4+ Interstitial Macrophages [scRNA-seq: mPL]

2023-03-03 | GSE225665 | GEO

Leukocyte Recruitment and iBALT Formation Require Chemokine-Secreting Pf4+ Interstitial Macrophages [scRNA-seq: hSk]

2023-03-03 | GSE225662 | GEO

Leukocyte Recruitment and iBALT Formation Require Chemokine-Secreting Pf4+ Interstitial Macrophages [scRNA-seq: mTumor]

Project description:Pulmonary resident macrophages consist of alveolar macrophages (AMs) and interstitial macrophages (IMs). While much is known about the role of AMs, the function of IMs, which are conserved across multiple organs and species, remains unclear. Using single-cell RNA sequencing (scRNA-seq) after inducing acute lung injury, we identified at least six distinct subtypes of pulmonary IMs, based on the chemokines they express. These subtypes are: IMck1 (Ccl2, Ccl7, Ccl12, a few Cxcl14); IMck2-4 (Ccl3, Ccl4, Ccl5, Cxcl2, Cxcl3); IMck5-7 (Ccl6, Ccl8, Ccl9); IMck8 (Cxcl9, Cxcl10); IMck9 (Cxcl13); and IMck10 (Ccl24). Based on the selective chemokine expression profiles observed, we hypothesized that pulmonary IMs play a critical role in recruiting leukocytes and forming inducible bronchus-associated lymphoid tissue (iBALT) in the lung. First, we examined multiple Cre-expressing mice (Lyve1, Nes, Pdpn, and Pf4) for IM specificity by crossing them with Rosa26EYFP. Only the Pf4Cre mice selectively induced EYFP expression in CD206hiCD64hi IMs, where no other immune cell in the lung expressed EYFP. We then created a CD206hiCD64hi IM-depleting mouse by crossing Pf4Cre with Rosa26DTR and CX3CR1_001DTR. In a bacterial infection and allergic airway disease, depletion of CD206hiCD64hi IMs resulted in diminished leukocyte recruitment and iBALT formation. Overall, our study highlights the increased granularity in IM populations and demonstrates a division of labor for cellular recruitment and iBALT formation in the lung. Furthermore, the study suggests that the specific combination of chemokines expressed by IMs are tightly regulated, like Th cytokine-producing cells.

2023-03-03 | GSE225667 | GEO

Leukocyte Recruitment and iBALT Formation Require Chemokine-Secreting Pf4+ Interstitial Macrophages [scRNA-seq: mLu]

2023-03-03 | GSE225664 | 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