Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Imaging mouse lung allograft rejection with (1)H MRI.

ABSTRACT: To demonstrate that longitudinal, noninvasive monitoring via MRI can characterize acute cellular rejection in mouse orthotopic lung allografts.Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig versus anti-CD4/anti-CD8 treated groups. A two-dimensional multislice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at postoperative days 3, 7, and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures.Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 posttransplantation (0.046?0.789; P?

SUBMITTER: Guo J

PROVIDER: S-EPMC4272671 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Imaging mouse lung allograft rejection with (1)H MRI.

Guo Jinbang J Huang Howard J HJ Wang Xingan X Wang Wei W Ellison Henry H Thomen Robert P RP Gelman Andrew E AE Woods Jason C JC

Magnetic resonance in medicine 20140620 5

<h4>Purpose</h4>To demonstrate that longitudinal, noninvasive monitoring via MRI can characterize acute cellular rejection in mouse orthotopic lung allografts.<h4>Methods</h4>Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig versus anti-CD4/anti-CD8 treated groups. A two-dimensional multislice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung a ...[more]

PMID: 24954886

Similar Datasets

Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection.

Project description:Lung transplantation is the only viable option for patients suffering from otherwise incurable end-stage pulmonary diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Despite aggressive immunosuppression, acute rejection of the lung allograft occurs in over half of transplant recipients, and the factors that promote lung acceptance are poorly understood. The contribution of lymphatic vessels to transplant pathophysiology remains controversial, and data that directly address the exact roles of lymphatic vessels in lung allograft function and survival are limited. Here, we have shown that there is a marked decline in the density of lymphatic vessels, accompanied by accumulation of low-MW hyaluronan (HA) in mouse orthotopic allografts undergoing rejection. We found that stimulation of lymphangiogenesis with VEGF-C156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection response and improves clearance of HA from the lung allograft. Longitudinal analysis of transbronchial biopsies from human lung transplant recipients demonstrated an association between resolution of acute lung rejection and decreased HA in the graft tissue. Taken together, these results indicate that lymphatic vessel formation after lung transplantation mediates HA drainage and suggest that treatments to stimulate lymphangiogenesis have promise for improving graft outcomes.

| S-EPMC4639995 | biostudies-literature

Blocking hyaluronan synthesis alleviates acute lung allograft rejection.

Project description:Lung allograft rejection results in the accumulation of low-molecular weight hyaluronic acid (LMW-HA), which further propagates inflammation and tissue injury. We have previously shown that therapeutic lymphangiogenesis in a murine model of lung allograft rejection reduced tissue LMW-HA and was associated with improved transplant outcomes. Herein, we investigated the use of 4-Methylumbelliferone (4MU), a known inhibitor of HA synthesis, to alleviate acute allograft rejection in a murine model of lung transplantation. We found that treating mice with 4MU from days 20 to 30 after transplant was sufficient to significantly improve outcomes, characterized by a reduction in T cell-mediated lung inflammation and LMW-HA content and in improved pathology scores. In vitro, 4MU directly attenuated activation, proliferation, and differentiation of naive CD4+ T cells into Th1 cells. As 4MU has already been demonstrated to be safe for human use, we believe examining 4MU for the treatment of acute lung allograft rejection may be of clinical significance.

| S-EPMC8663774 | biostudies-literature

Gut Microbiota Can Impact Chronic Murine Lung Allograft Rejection.

Project description: Not available

| S-EPMC6348725 | biostudies-literature

IL-27R?: A Novel Molecular Imaging Marker for Allograft Rejection.

Project description:Non-invasively monitoring allogeneic graft rejection with a specific marker is of great importance for prognosis of patients. Recently, data revealed that IL-27R? was up-regulated in alloreactive CD4+ T cells and participated in inflammatory diseases. Here, we evaluated whether IL-27R? could be used in monitoring allogeneic graft rejection both in vitro and in vivo. Allogeneic (C57BL/6 donor to BALB/c recipient) and syngeneic (BALB/c both as donor and recipient) skin grafted mouse models were established. The expression of IL-27R? in grafts was detected. The radio-probe, 125I-anti-IL-27R? mAb, was prepared. Dynamic whole-body phosphor-autoradiography, ex vivo biodistribution and immunofluorescence staining were performed. The results showed that the highest expression of IL-27R? was detected in allogeneic grafts on day 10 post transplantation (top period of allorejection). 125I-anti-IL-27R? mAb was successfully prepared with higher specificity and affinity. Whole-body phosphor-autoradiography showed higher radioactivity accumulation in allogeneic grafts than syngeneic grafts on day 10. The uptake of 125I-anti-IL-27R? mAb in allogeneic grafts could be almost totally blocked by pre-injection with excess unlabeled anti-IL-27R? mAb. Interestingly, we found that 125I-anti-IL-27R? mAb accumulated in allogeneic grafts, along with weaker inflammation earlier on day 6. The high uptake of 125I-anti-IL-27R? mAb was correlated with the higher infiltrated IL-27R? positive cells (CD3+/CD68+) in allogeneic grafts. In conclusion, IL-27R? may be a novel molecular imaging marker to predict allorejection.

| S-EPMC7072931 | biostudies-literature

Donor-Derived Exosomes With Lung Self-Antigens in Human Lung Allograft Rejection.

Project description:The immunological role of exosomes in allograft rejection remains unknown. We sought to determine whether exosomes are induced during lung allograft rejection and to define the antigenic compositions of HLA, lung-associated self-antigens (SAgs) and microRNAs (miRNAs). Exosomes were isolated from sera and bronchoalveolar lavage fluid from 30 lung transplant recipients (LTxRs) who were stable or who had acute rejection (AR) or bronchiolitis obliterans syndrome (BOS). Exosomes were defined by flow cytometry for CD63 and western blotting for annexin V SAgs, collagen V (Col-V) and Kα1 tubulin were examined by electron microscopy; miRNAs were profiled by a miRNA array. Donor HLA and SAgs were detected on exosomes from LTxRs with AR and BOS but not from stable LTxRs. Exosomes expressing Col-V were isolated from sera from LTxRs 3 mo before AR and 6 mo before BOS diagnosis, suggesting that exosomes with SAgs may be a noninvasive rejection biomarker. Exosomes isolated from LTxRs with AR or BOS also contained immunoregulatory miRNAs. We concluded that exosomes expressing donor HLA, SAgs and immunoregulatory miRNAs are present in the circulation and local site after human lung transplantation and play an important role in the immune pathogenesis of acute allograft rejection and BOS.

| S-EPMC5340154 | biostudies-literature

Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection.

Project description:Supplementary methods to identify acute rejection and to distinguish rejection from infection may improve clinical outcomes for lung allograft recipients. We hypothesized that distinct bronchoalveolar lavage (BAL) cell profiles are associated with rejection and infection. We retrospectively compared 2939 BAL cell counts and immunophenotypes against concomitantly obtained transbronchial biopsies and microbiologic studies. We randomly assigned 317 subjects to a derivation or validation cohort. BAL samples were classified into four groups: infection, rejection grade ?A1, both or neither. We employed generalized estimating equation and survival modeling to identify clinical predictors of rejection and infection. We found that CD25(+) and natural killer cell percentages identified a twofold increased odds of rejection compared to either the infection or the neither infection nor rejection groups. Also, monocytes, lymphocytes and eosinophil percentages were independently associated with rejection. A four-predictor scoring system had high negative predictive value (96-98%) for grade ?A2 rejection, predicted future rejection in the validation cohort and predicted increased risk of bronchiolitis obliterans syndrome in otherwise benign samples. In conclusion, BAL cell immunophenotyping discriminates between infection and acute rejection and predicts future outcomes in lung transplant recipients. Although it cannot replace histopathology, immunophenotyping may be a clinically useful adjunct.

| S-EPMC4300200 | biostudies-literature

Blocking hyaluronan synthesis alleviates acute lung allograft rejection.

Project description:Lung allograft rejection results in the accumulation of low molecular weight hyaluronic acid (LMW-HA), which further propagates inflammation and tissue injury. We have previously shown that therapeutic lymphangiogenesis in a murine model of lung allograft rejection reduced tissue LMW-HA and was associated with improved transplant outcomes. Herein we investigated the use of 4-Methylumbelliferone (4-MU), a known inhibitor of HA synthesis, to alleviate acute allograft rejection in a murine model of lung transplantation. We found that treating mice with 4-MU from day 20-30 post-transplant was sufficient to significantly improve outcomes, characterized by a reduction in T-cell mediated lung inflammation, LMW-HA content and improved pathology scores. In vitro, 4-MU directly attenuated activation, proliferation, and differentiation of naïve CD4+ T-cells into Th1 cells. As 4-MU has already been demonstrated to be safe for human use, we believe examining 4-MU for the treatment of acute lung allograft rejection may be of clinical significance.

2021-12-15 | GSE183142 | GEO

Inhibitory effects of pirfenidone on dendritic cells and lung allograft rejection.

Project description:Pirfenidone (PFD) is an antifibrotic agent with beneficial effects on proinflammatory disorders. In this study, we further investigated PFD and long-acting form, "deuterated PFD," immune-modulating properties by evaluating their effects on mouse dendritic cells (DCs).The effects of PFD on DCs were examined in vivo using an orthotopic mouse lung transplant model and in vitro using isolated bone marrow-derived DCs in response to lipopolysaccharide and allogeneic stimulation.In mouse lung transplants, PFD and deuterated PFD treatment improved allograft lung function based on peak airway pressure, less infiltrates/consolidation on micro-computed tomography scan imaging, and reduced lung rejection/injury. DC activation from lung allografts was suppressed with PFD, and there seemed to be a greater effect of PFD on CD11c(+)CD11b(-)CD103(+) lung DCs. In addition, PFD reduced the expression of several proinflammatory cytokines/chemokines from lung allografts. In vitro, DCs treated with PFD showed decreased expression of major histocompatibility complex class II and costimulatory molecules and the capacity of these DCs to stimulate T-cell activation was impaired, although antigen uptake was preserved. PFD directly inhibited the release of inflammatory cytokines from isolated DCs, was associated with a reduction of stress protein kinases, and attenuated lipopolysaccharide-dependent mitogen-activated protein kinase p38 phosphorylation.PFD has lung allograft protective properties, and in addition to its known effects on T-cell biology, PFD immune-modulating activities encompass inhibitory effects on DC activation and function.

| S-EPMC3402635 | biostudies-literature

Cutting edge: Acute lung allograft rejection is independent of secondary lymphoid organs.

Project description:It is the prevailing view that adaptive immune responses are initiated in secondary lymphoid organs. Studies using alymphoplastic mice have shown that secondary lymphoid organs are essential to initiate allograft rejection of skin, heart, and small bowel. The high immunogenicity of lungs is well recognized and allograft rejection remains a major contributing factor to poor outcomes after lung transplantation. We show in this study that alloreactive T cells are initially primed within lung allografts and not in secondary lymphoid organs following transplantation. In contrast to other organs, lungs are acutely rejected in the absence of secondary lymphoid organs. Two-photon microscopy revealed that recipient T cells cluster predominantly around lung-resident, donor-derived CD11c(+) cells early after engraftment. These findings demonstrate for the first time that alloimmune responses following lung transplantation are initiated in the graft itself and therefore identify a novel, potentially clinically relevant mechanism of lung allograft rejection.

| S-EPMC3760174 | biostudies-literature

Therapies for Chronic Allograft Rejection.

Project description:Remarkable advances have been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) over the past decades, leading to improved graft outcomes. However, long-term failure is still high and effective treatment for chronic ABMR, an important cause of graft failure, has not yet been identified. Chronic ABMR has a relatively different phenotype from active ABMR and is a slowly progressive disease in which graft injury is mainly caused by de novo donor specific antibodies (DSA). Since most trials of current immunosuppressive therapies for rejection have focused on active ABMR, treatment strategies based on those data might be less effective in chronic ABMR. A better understanding of chronic ABMR may serve as a bridge in establishing treatment strategies to improve graft outcomes. In this in-depth review, we focus on the pathophysiology and characteristics of chronic ABMR along with the newly revised Banff criteria in 2017. In addition, in terms of chronic ABMR, we identify the reasons for the resistance of current immunosuppressive therapies and look at ongoing research that could play a role in setting better treatment strategies in the future. Finally, we review non-invasive biomarkers as tools to monitor for rejection.

| S-EPMC8082459 | biostudies-literature

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