Summary of Study ST001255
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000841. The data can be accessed directly via it's Project DOI: 10.21228/M8011M This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST001255 |
Study Title | Immunomodulatory activity of hyaluronidase is associated with metabolic adaptations during acute inflammation |
Study Summary | Objective and design: Investigate survival outcomes, and immunological and metabolomic effects of hyaluronidase (Hz) treatment during mouse models of acute inflammation and sepsis. Methods: Survival of C57Bl/6 mice was monitored after lethal challenge with lipopolysaccharide (LPS) or cecal and ligation puncture (CLP)-induced sepsis and treated with Hz or saline. Mice were also challenged with LPS and treated with Hz for leukocyte counting, cytokine quantification and determination of metabolomic profiles in the peritoneal fluid. Results: Hz treatment improved survival outcomes after lethal challenge with LPS or CLPinduced sepsis. LPS challenge promoted acute neutrophil accumulation and production of interleukin-1β (IL-1β) and IL-6 in the peritoneum, whereas Hz treatment suppressed neutrophil infiltration and cytokine production. We further characterized the metabolomic alterations caused by LPS challenge, which predicted activity of metabolic pathways related to fatty acids and eicosanoids. Hz treatment had a profound effect over the metabolic response, reflected by reductions of the relative levels of fatty acids. Conclusion: Collectively, these data demonstrate that Hz treatment is associated with metabolic reprogramming of pathways that sustain the inflammatory response. |
Institute | Sao Paulo University |
Department | School of Pharmaceutical Sciences of Ribeirao Preto |
Last Name | Gardinassi |
First Name | Luiz Gustavo |
Address | Av do Cafe, s/n - Ribeirão Preto - SP |
gustavogardinassi@usp.br | |
Phone | 551633154189 |
Submit Date | 2019-09-26 |
Num Groups | 8 |
Total Subjects | 40 |
Num Males | 40 |
Raw Data Available | Yes |
Raw Data File Type(s) | wiff |
Analysis Type Detail | LC-MS |
Release Date | 2019-10-11 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
Project ID: | PR000841 |
Project DOI: | doi: 10.21228/M8011M |
Project Title: | Immunomodulatory activity of hyaluronidase is associated with metabolic adaptations during acute inflammation |
Project Type: | Untargeted MS |
Project Summary: | Objective and design: Investigate survival outcomes, and immunological and metabolomic effects of hyaluronidase (Hz) treatment during mouse models of acute inflammation and sepsis. Methods: Survival of C57Bl/6 mice was monitored after lethal challenge with lipopolysaccharide (LPS) or cecal and ligation puncture (CLP)-induced sepsis and treated with Hz or saline. Mice were also challenged with LPS and treated with Hz for leukocyte counting, cytokine quantification and determination of metabolomic profiles in the peritoneal fluid. Results: Hz treatment improved survival outcomes after lethal challenge with LPS or CLPinduced sepsis. LPS challenge promoted acute neutrophil accumulation and production of interleukin-1β (IL-1β) and IL-6 in the peritoneum, whereas Hz treatment suppressed neutrophil infiltration and cytokine production. We further characterized the metabolomic alterations caused by LPS challenge, which predicted activity of metabolic pathways related to fatty acids and eicosanoids. Hz treatment had a profound effect over the metabolic response, reflected by reductions of the relative levels of fatty acids. Conclusion: Collectively, these data demonstrate that Hz treatment is associated with metabolic reprogramming of pathways that sustain the inflammatory response. |
Institute: | Sao Paulo University |
Department: | Department of Clinical Analyses, Toxicology and Food Sciences |
Last Name: | Gardinassi |
First Name: | Luiz Gustavo |
Address: | Av do Café s/n - Ribeirão Preto - SP |
Email: | gustavogardinassi@usp.br |
Phone: | 551633154189 |
Funding Source: | FAPESP; CNPq; CAPES |
Subject:
Subject ID: | SU001323 |
Subject Type: | Mammal |
Subject Species: | Mus musculus |
Taxonomy ID: | 10090 |
Genotype Strain: | C57Bl6 |
Weight Or Weight Range: | 22–25 g |
Gender: | Male |
Animal Light Cycle: | light/dark cycle |
Animal Feed: | Ad libitum |
Animal Water: | Ad libitum |
Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
mb_sample_id | local_sample_id | Treatment | Time |
---|---|---|---|
SA091259 | Hz_27h_4 | Hz | 27h |
SA091260 | Hz_27h_3 | Hz | 27h |
SA091261 | Hz_27h_2 | Hz | 27h |
SA091262 | Hz_27h_6 | Hz | 27h |
SA091263 | Hz_27h_5 | Hz | 27h |
SA091264 | Hz_7d_5 | Hz | 7d |
SA091265 | Hz_7d_1 | Hz | 7d |
SA091266 | Hz_7d_3 | Hz | 7d |
SA091267 | Hz_7d_6 | Hz | 7d |
SA091268 | Hz_7d_2 | Hz | 7d |
SA091269 | LPS_Hz_27h_1 | LPS + Hz | 27h |
SA091270 | LPS_Hz_27h_6 | LPS + Hz | 27h |
SA091271 | LPS_Hz_27h_4 | LPS + Hz | 27h |
SA091272 | LPS_Hz_27h_3 | LPS + Hz | 27h |
SA091273 | LPS_Hz_27h_2 | LPS + Hz | 27h |
SA091274 | LPS_Hz_27h_5 | LPS + Hz | 27h |
SA091275 | LPS_Hz_7d_1 | LPS + Hz | 7d |
SA091276 | LPS_Hz_7d_3 | LPS + Hz | 7d |
SA091277 | LPS_Hz_7d_2 | LPS + Hz | 7d |
SA091278 | LPS_27h_6 | LPS | 27h |
SA091279 | LPS_27h_1 | LPS | 27h |
SA091280 | LPS_27h_5 | LPS | 27h |
SA091281 | LPS_27h_3 | LPS | 27h |
SA091282 | LPS_27h_2 | LPS | 27h |
SA091283 | LPS_3h_1 | LPS | 3h |
SA091284 | LPS_3h_2 | LPS | 3h |
SA091285 | LPS_3h_5 | LPS | 3h |
SA091286 | LPS_3h_6 | LPS | 3h |
SA091287 | LPS_3h_4 | LPS | 3h |
SA091288 | LPS_3h_3 | LPS | 3h |
SA091289 | LPS_7d_6 | LPS | 7d |
SA091290 | LPS_7d_1 | LPS | 7d |
SA091291 | LPS_7d_3 | LPS | 7d |
SA091292 | LPS_7d_2 | LPS | 7d |
SA091293 | LPS_7d_4 | LPS | 7d |
SA091294 | LPS_7d_5 | LPS | 7d |
SA091295 | PBS_2 | PBS | 0h |
SA091296 | PBS_3 | PBS | 0h |
SA091297 | PBS_4 | PBS | 0h |
SA091298 | PBS_1 | PBS | 0h |
Showing results 1 to 40 of 40 |
Collection:
Collection ID: | CO001317 |
Collection Summary: | Mice were anesthetized with ketamine (100mg/kg) (Dopaser®, Minas Gerais, Brazil) and xylazine (10mg/kg) (Agener União, São Paulo, Brazil). Following euthanasia in CO2 chamber, 3mL of PBS was added into the abdominal cavity, which was gently massaged for 1 min. The peritoneal fluid was collected with a needle inserted into the inguinal region. |
Sample Type: | Peritoneal fluid |
Storage Conditions: | -80℃ |
Treatment:
Treatment ID: | TR001338 |
Treatment Summary: | Endotoxemia was induced in mice by intraperitoneal (i.p.) injection of LPS dissolved in 0.3 mL of phosphate-buffered saline (PBS). Control groups received sterile PBS. Tree hours (h) after LPS injection, mice were treated with 16 U of Hz (dissolved in 0.3 mL of PBS) every 8 h |
Sample Preparation:
Sampleprep ID: | SP001331 |
Sampleprep Summary: | Peritoneal fluid samples were spiked with stable isotope internal standards and metabolites were enriched with solid phase extraction cartridges (Hypersep C18-500 mg, 3 mL, Thermo Scientific-Bellefonte, PA, USA) and methanol/water as solvents. |
Combined analysis:
Analysis ID | AN002084 |
---|---|
Analysis type | MS |
Chromatography type | Reversed phase |
Chromatography system | Shimadzu Nexera X2 |
Column | Ascentis Express C18 (100 x 4.6mm,2.7um) |
MS Type | ESI |
MS instrument type | Triple TOF |
MS instrument name | ABI Sciex 5600 TripleTOF |
Ion Mode | NEGATIVE |
Units | peak intensity |
Chromatography:
Chromatography ID: | CH001521 |
Chromatography Summary: | Reversed-phase chromatography was accomplished with a 100 × 4.6 mm, 2.7 μm Ascentis Express C18 column (Supelco - St. Louis, MO, USA) with an Ultra-High-Performance Liquid Chromatography (UHPLC) system (Nexera X2, Shimadzu-Kyoto, HO, Japan). The gradient consisted of Phase A, H2O/ACN/acetic acid (69.98:30:0.02, v/v/v) at pH 5.8 (adjusted with NH4OH), and Phase B, an ACN/isopropanol (70:30, v/v). Gradient elution was carried out for 25 min at a flow rate of 0.6 mL. / min. Gradient conditions were as follows: 0 to 2.0 min, 0% B; 2.0 to 5.0 min, 15% B; 5.0 to 8.0 min, 20% B; 8.0 to 11.0 min, 35% B; 11.0 to 15.0 min, 70% B; and 15.0 to 19 min, 100% B. At 19.0 min, the gradient returned to the initial condition of 0% B, and the column was re-equilibrated until 25.0 min. |
Methods Filename: | PR_CH_Methods.pdf |
Instrument Name: | Shimadzu Nexera X2 |
Column Name: | Ascentis Express C18 (100 x 4.6mm,2.7um) |
Flow Gradient: | 0 to 2.0 min, 0% B; 2.0 to 5.0 min, 15% B; 5.0 to 8.0 min, 20% B; 8.0 to 11.0 min, 35% B; 11.0 to 15.0 min, 70% B; and 15.0 to 19 min, 100% B. At 19.0 min, the gradient returned to the initial condition of 0% B, and the column was re-equilibrated until 25.0 min. |
Flow Rate: | 0.6ml/min |
Solvent A: | 70% water/30% acetonitrile; 0.02% acetic acid, pH 5.8(adjusted with ammonium hydroxide) |
Solvent B: | 70% acetonitrile/30% isopropanol |
Chromatography Type: | Reversed phase |
MS:
MS ID: | MS001935 |
Analysis ID: | AN002084 |
Instrument Name: | ABI Sciex 5600 TripleTOF |
Instrument Type: | Triple TOF |
MS Type: | ESI |
MS Comments: | Mass spectral data was acquired with negative electrospray ionization and the full scan of mass-to-charge ratio (m/z) ranged from 100 to 1500. Proteowizard software was used to convert wiff files into mzXML files. Peak peaking, noise filtering, retention time and m/z alignment, and feature quantification were performed with apLCMS. Three parameters define a metabolite feature: mass-to-charge ratio (m/z), retention time and intensity values. Data were log2 transformed and only features detected in at least 80% of samples from one group (5439 m/z features) were used in further analysis. Missing values were imputed using half mean of the feature across all samples. The mummichog software (version 2) was used for metabolic pathway enrichment analysis (mass accuracy under 10 ppm). |
Ion Mode: | NEGATIVE |