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Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation

ABSTRACT: Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation

PROVIDER: PRJNA590495 | ENA |

REPOSITORIES: ENA

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Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation

Project description:Primary graft dysfunction (PGD) is the leading cause of early mortality after lung transplantation. Anti-collagen type-V (col(V)) immunity has been observed in animal models of ischemia-reperfusion injury (IRI) and in PGD. We hypothesized that collagen type-V is an innate danger signal contributing to PGD pathogenesis. Methods: Anti-col(V) antibody production was detected by flow cytometric assay following cultures of murine CD19+ splenic cells with col(V). Responding murine B cells were phenotyped using surface markers. RNA-Seq analysis was performed on murine CD19+ cells. Levels of anti-col(V) antibodies were measured in 188 recipients from the Lung Transplant Outcomes Group (LTOG) after transplantation. Results: Col(V) induced rapid production of anti-col(V) antibodies from murine CD19+ B cells. Subtype analysis demonstrated innate B-1 B cells bound col(V). Col(V) induced a specific transcriptional signature in CD19+ B cells with similarities to, yet distinct from, B cell receptor (BCR) stimulation. Rapid de novo production of anti-col(V) Abs was associated with an increased incidence of clinical PGD after lung transplant. Conclusions: This study demonstrated that col(V) is an rapidly recognized by B cells and has specific transcriptional signature. In lung transplants recipients the rapid seroconversion to anti-col(V) Ab is linked to increased risk of grade 3 PGD.

2019-11-20 | GSE140681 | GEO

Transcription profiling of human monocytes exposed to lipopolysaccharide or collagen-related peptide to elucidate the transcriptional differences in monocytes responding to either a danger or damage signal

Project description:stimulation of whole blood using 5 ng/ml lipopolysaccharide (LPS, gram -ve bacterial endotoxin) or 5 ug/ml CRP-18 (collagen-related peptide; GPO-18). Monocytes respond to stimuli differently. This experiment was designed to elucidate the transcriptional differences in monocytes responding to either a danger signal (supplied by LPS) or a damage signal (supplied by CRP-18). CRP-18 is a collagen mimetic and was used to represent collagen exposure at sites of vessel damage. Exposed collagen activates platelts which in turn activate monocytes. The transcriptional differences which ensue are not known yet and were investigated in this work.

2010-01-01 | E-TABM-483 | biostudies-arrayexpress

Danger signal initiates differentiation of monocytes into osteopontin‑producing macrophages III

Project description:Purpose: We report the application of single-cell RNA sequencing for profiling the genexpression of different monocyte types in order to characterize monocytes that differentiate into macrophages under danger signal in comparison to conventional GM-CSF and M-CSF macrophages Methods: Monocytes freshly isolated from PBMCs were differentiated into GM-CSF, M-CSF, and danger-signal induced macrophages. Two million cells of each macrophage population were tagged accordingly with TotalSeq™‑B Hashtags. Single cell RNA sequencing was performed on all macrophage populations in order to characterize cells from each population. ScRNAseq analysis was performed with the R package Seurat on 16470 barcodes after filtering. Results: Cluster analysis reveals distinct separation of all three macrophage populations. Conclusion: The clear difference in overall gene expression profile suggests that macrophages exposed to danger signal differentiate into a novel macrophage type in contrast to conventional GM-CSF and M-CSF monocytes.

2022-01-11 | GSE180113 | GEO

Danger signal initiates differentiation of monocytes into osteopontin‑producing macrophages

Project description:Analysis of gene expression of monocytes differentiating into macrophages in the presence of a danger signal. Kinetic analysis (1 day, 2 days, 4 days, 7 days) and analysis of lipopolysaccharide stimulated 7 day macrophages in comparison to unstimulated 7 day macrophages.

2022-01-11 | GSE180027 | GEO

Danger signal initiates differentiation of monocytes into osteopontin‑producing macrophages

Project description:Danger signal initiates differentiation of monocytes into osteopontin‑producing macrophages

| PRJNA746299 | ENA

Danger signal initiates differentiation of monocytes into osteopontin‑producing macrophages III

Project description:Danger signal initiates differentiation of monocytes into osteopontin‑producing macrophages III

| PRJNA746582 | ENA

Danger signal initiates differentiation of monocytes into osteopontin‑producing macrophages II

Project description:Danger signal initiates differentiation of monocytes into osteopontin‑producing macrophages II

| PRJNA746583 | ENA

Donor lung tissues: Control vs. Primary graft dysfunction (PGD)

Project description:Primary graft dysfunction (PGD) continues to be a major cause of early death after lung transplantation. Moreover, there remains a lack of accurate pre-transplant molecular markers for predicting PGD. To identify distinctive gene expression signatures associated with PGD, we profiled human donor lungs using microarray technology prior to the graft implantation. The genomic profiles of 10 donor lung samples from patients who subsequently developed clinically defined severe PGD were compared with 16 case-matched donor lung samples from those who had a favorable outcome without PGD. Matched factors used were: recipient age (Â± 10 years), recipient gender, recipient lung disease, and type of transplantation (single or bilateral). Keywords: Observational case-control study Matched case-control observational study: 10 primary graft dysfunction cases vs 16 Good outcome cases. One replicate per array.

2008-09-15 | E-GEOD-9102 | biostudies-arrayexpress

Macrophage infiltration induced by donor hypovolemia protects against severe primary graft dysfunction in mouse lung transplantation

Project description:BACKGROUND: Hypovolemia is common in lung donors before or after brain death. However, its impact on primary graft function (PGD) remains obscure. METHODS: A clinically relevant two-hit model of PGD was established by integrating hypovolemic shock (HS) and cold ischemia-reperfusion in a mouse model of orthotopic lung transplantation (LTx) from C57BL/6 to Balb/c. At -48 hours, HS was induced to donor by withdrawal of blood from femoral artery and keeping the mean arterial pressure at 15±5 mmHg for 4 h. At -24 hours, donor lungs were retrieved from mice with or without HS and stored at 0ºC until transplantation. CD11b-DTR mice were used as donor and treated with Diphtheria Toxin (DT) to deplete graft-infiltrating macrophages. RESULTS: HS mainly caused macrophage-predominant infiltration around pulmonary artery injury systemic inflammatory response, but little impairment of lung function even if in combination with cold ischemia-reperfusion. Transcriptional profiling showed HS pretreatment increased pulmonary damage and alveolar remodeling but ameliorated inflammatory infiltration when compared to one-hit model of 12 hours cold ischemia-reperfusion injury. The allografts with donor DT-treatment one day ahead of HS showed injury and dysfunction at donation and worsened further at 24 hours reperfusion, whereas the allografts with recipient DT-treatment immediately after transplantation showed similar function and histology to the control treated with saline. CONCLUSION: Donor hypovolemia causes pulmonary artery injury and infiltration but has little impact on allograft function, even in combination with 24 h cold ischemia. Graft-infiltrating macrophages are critical in protecting graft from HS-induced injury and cold ischemia-reperfusion injury.

2022-03-30 | GSE156322 | GEO

RNA-seq of bronchoalveolar lavage samples of lung transplant primary graft dysfunction

Project description:This is an RNA-seq study of human lung transplant recipients. Bronchoalveolar lavage cells were collected on the first day after lung transplant. We performed bulk RNA-sequencing on 19 lung transplant recipients with severe primary graft dysfunction (PGD) and 19 lung transplant recipients without primary graft dysfunction. As this data is human identifiable, raw data are not included in this record.

2023-02-15 | E-MTAB-12282 | biostudies-arrayexpress

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