Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE208233 | GEO | 2022/12/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Smith2011 - Three Stage Innate Immune Response to a Pneumococcal Lung Infection

Project description:Pneumococcal pneumonia is a leading cause of death and a major source of human morbidity. The initial immune response plays a central role in determining the course and outcome of pneumococcal disease. We combine bacterial titer measurements from mice infected with Streptococcus pneumoniae with mathematical modeling to investigate the coordination of immune responses and the effects of initial inoculum on outcome. To evaluate the contributions of individual components, we systematically build a mathematical model from three subsystems that describe the succession of defensive cells in the lung: resident alveolar macrophages, neutrophils and monocyte-derived macrophages. The alveolar macrophage response, which can be modeled by a single differential equation, can by itself rapidly clear small initial numbers of pneumococci. Extending the model to include the neutrophil response required additional equations for recruitment cytokines and host cell status and damage. With these dynamics, two outcomes can be predicted: bacterial clearance or sustained bacterial growth. Finally, a model including monocyte-derived macrophage recruitment by neutrophils suggests that sustained bacterial growth is possible even in their presence. Our model quantifies the contributions of cytotoxicity and immune-mediated damage in pneumococcal pathogenesis.

2024-09-02 | BIOMD0000000924 | BioModels

Reprogrammed alveolar macrophages after pneumonia recovery

Project description:Community-acquired pneumonia is a widespread disease with significant morbidity and mortality. Alveolar macrophages are tissue-resident lung cells that play a crucial role in innate immunity against bacteria causing pneumonia. We hypothesized that alveolar macrophages display adaptive characteristics after resolution of bacterial pneumonia. We studied mice one to six months after self-limiting lung infection due to Streptococcus pneumoniae, the most common cause of bacterial pneumonia. Among the myeloid cells recovered from the lung, only alveolar macrophages showed long-term modifications of their surface marker phenotype. The remodeling of alveolar macrophages was: (i) long-lasting (still observed 6 months post infection), (ii) regionally localized (only observed in the affected lobe after lobar pneumonia), and (iii) associated with a macrophage-dependent enhanced lung protection to another pneumococcal serotype. Metabolomic and transcriptomic profiling revealed that alveolar macrophages of mice which recovered from pneumonia had new baseline activities and altered responses to infection. Thus, the enhanced lung protection after mild and self-limiting respiratory infection includes a profound remodeling of alveolar macrophages that is long-lasting, compartmentalized, and manifest across surface receptors, metabolites, and both resting and stimulated transcriptomes. We used microarrays to detail the global program of gene expression for mouse alveolar macrophages sorted from lungs that were naïve or infected more than a month previously, at rest and during an acute (4-hour) infection.

2020-04-17 | GSE133975 | GEO

SAGE analysis of alveolar macrophages from metastatic lung and untreated lung

Project description: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.

2018-02-16 | GSE106987 | GEO

Insights into Early Recovery from Influenza Pneumonia by Spatial and Temporal Quantification of Putative Lung Regeneration Cells and buy Lung Proteomics

Project description:During influenza pneumonia, the alveolar epithelial cells of the lungs are targeted by influenza virus. The distal airway stem cells (DASCs) and proliferating alveolar type II (AT2) cells are reported to be putative lung repair cells. However, their relative spatial and temporal distribution is still unknown during influenza-induced acute lung injury. Here, we investigated the distribution of these cells, and concurrently performed global proteomic analysis of the infected lungs to elucidate and link the cellular and molecular events during influenza pneumonia recovery. BALB/c mice were infected with a sub-lethal dose of influenza H1N1 virus. From 5 to 25 days post-infection (dpi), mouse lungs were subjected to histopathologic and immunofluorescence analysis to probe for global distribution of lung repair cells (using P63 and KRT5 markers for DASCs; PCNA and SPC markers for AT2 cells). At 7 and 15 dpi, infected mouse lungs were also subjected to protein mass spectrometry for relative protein quantification. DASCs appeared only in the damaged area of the lung from 7 dpi onwards, reaching a peak at 21 dpi, and persisted at 25 dpi. However, no differentiation of DASCs to AT2 cells was observed by 25 dpi. In contrast, AT2 cells began proliferating from 7 dpi to replenish its population. Mass spectrometry and gene ontology analysis revealed prominent innate immune response at 7 dpi, which shifted towards adaptive immune responses by 15 dpi. Hence, proliferating AT2 cells but not DASCs contribute to AT2 cell regeneration following transition from innate to adaptive immune responses during the early phase of recovery from influenza pneumonia up to 25 dpi.

2020-04-17 | PXD014967 | Pride

Nogo-B protects mice against lipopolysaccharide-induced acute lung injury

Project description:Purpose: Acute lung injury (ALI) is a severe clinical disorder characterized by diffused capillary-alveolar barrier damage and noncardiogenic lung edema induced by excessive inflammation reactions. Nogo-B, a member of the reticulon 4 protein family, plays a critical role in modulating macrophages and neutrophils’ function in inflammation. Its role in ALI remains unclear. Methods: Pulmonary expression of Nogo-B was investigated in a LPS-induced ALI mice model. The effects and the underline mechanisms of Nogo-B expression on the severity of lung injury was assessed using histological examination, Bronchoalveolar lavage fluid (BALF) protein and inflammatory cells and cytokines measurement, and microarray analysis. Results: Nogo-B was normally highly expressed in the lungs of naïve C57BL/6 mice. Intra-tracheal instillation of LPS significantly repressed the Nogo-B expression in lung tissues and BALF cells of ALI mice. In addition, over-expression of pulmonary Nogo-B using an adenovirus vector which expresses a Nogo-B-RFP-3-flag fusion protein (Ad-Nogo-B) significantly prolonged the survival time of mice challenged with lethal dose of LPS. Histological results and BALF protein measurement convinced that Ad-Nogo-B treated mice had less severity of lung injury and alveolar protein exudation, as compared with control adenovirus treated mice (Ad-RFP). They also had higher MCP-1 secretion and alveolar macrophages infiltration, but lower neutrophils infiltration. Finally, using microarray analysis, we identified a protective gene, PTX3, was highly elevated in Ad-Nogo-B treated mice. Conclusions: Nogo-B played a protective role in LPS-induced ALI, which might exert its role through modulation of inflammatory response and PTX3 secretion. A total of 12 samples from mice treated with or without LPS in the presence of Ad-Nogo-B or Ad-RFP transfection (n=3 for each group)

2013-07-12 | E-GEOD-48787 | biostudies-arrayexpress

Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia [whole lung]

Project description:The transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs. These studies tested the role of Nrf2 during pneumonia induced by Streptococcus pneumoniae (SP) at 24 hours in mice and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils.

2016-09-09 | GSE83612 | GEO

Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia [neutrophils]

2016-09-09 | GSE83613 | GEO

Emergence of CCL18- and IFI27-expressing macrophages in aging lungs, and potential roles for alveolar type 2 cell AGTR2 and macrophage BSG and CTSL expression in COVID-19

Project description:Aging lungs are associated with several lung diseases, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and pneumonia. This latter age-associated complication has been particularly prominent in the recent COVID-19 pandemic. We have analyzed carefully selected normal lung samples from human subjects at different ages simultaneously using hashtag-labeled samples and single cell RNA-sequencing technology. We identify prominent changes in macrophage populations in lungs from older individuals, including an emerging populations of macrophages expressing IFI27 and other interferon-regulated genes. We also see increased gene expression of CCL18 and other chemokines in FABP4+/alveolar and SPP1+/interstitial macrophages. All three macrophage populations highly express BSG/CD147a putative SARS-CoV-2 receptor and CSTL, a gene associated with SARS-CoV-2 activation. ACE2, the SARS-CoV-2 receptor, and TMPSS2, a SARS-CoV2 protease activator, are both expressed highly on AT2 cells with increased expression on AT2 cells from older lungs. AGTR2, a recently proposed alternative receptor for SARS-CoV-2 was highly selectively and markedly upregulated by AT2 cells from aging lungs. Thus, our data show increased lung expression of ACE2, AGTR2 and TMPRSS2 by AT2 cells with aging. In addition, our data indicate a distinct molecular pathway for lung SARS-CoV-2 infection of lung macrophages. Macrophages may contribute to increased COVID-19 severity in older patients by specific macrophage populations poised to contribute to the cytokine storm, in particular through enhanced interferon responses and interleukin-6 production.

2024-05-06 | GSE150148 | GEO

Infiltration of inflammatory macrophages and neutrophils and widespread pyroptosis in lung drive influenza lethality in nonhuman primates

Project description:We established a model by which precise doses of H5N1 influenza could be delivered via aerosol into the lower lungs of macaques. We then allowed the animals to progress to an endpoint, collected organs, sorted cells, and performed RNA seq specifically on whole lung, interstitial macrophages, alveolar macrophages or neutrophils.

2023-02-14 | GSE225316 | GEO

Leukocyte kinetics and bacterial clearance during S. pneumoniae pneumonia and contributions of ICAM-1

Project description:Streptococcus pneumoniae is a leading cause of community-acquired pneumonia. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that is highly expressed on the pulmonary capillary endothelium, alveolar epithelium and other cell types within the lung. ICAM-1 is known to play important roles in leukocyte adhesion, migration, and motility. To determine the contributions of ICAM-1 to bacterial clearance and leukocyte kinetics during pneumonia, mice were inoculated with S. pneumoniae and evaluated 1, 4 and 7 days later. Our results show that Icam1-/- mice have a greater number of viable bacteria within the lung at each time point. The impaired clearance observed in Icam1-/- mice was not due to an impediment in leukocyte recruitment. In fact, Icam1-/- mice had a greater number of neutrophils and recruited inflammatory macrophages in the lung tissue and the alveoli/airways on day 7. In contrast, fewer alveolar macrophages were present in the BAL of Icam1-/- mice. The loss of body weight and the concentrations of inflammatory mediators in the BAL were also significantly greater in Icam1-/- mice. Mechanistic studies to understand the defect in clearance show that neutrophils and macrophage subpopulations had no defect in phagocytosis or acidification of phagosomes. RNA sequencing reveals many differences in gene expression, but does not suggest° a defect in phagocytosis. Thus, ICAM-1 is necessary for the clearance of S. pneumoniae and for the resolution of pneumonia, but is not required for the recruitment of neutrophils or inflammatory macrophages into the pneumonic lung parenchyma or the alveoli/airways during S. pneumoniae-induced pneumonia.

2024-10-16 | GSE270761 | 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