Summary of project PR001576
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 PR001576. The data can be accessed directly via it's Project DOI: 10.21228/M80709 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001576 |
| Project DOI: | doi: 10.21228/M80709 |
| Project Title: | Mouse Neutrophil NTEM eicosanoids WT vs KI vs KO |
| Project Summary: | Uncontrolled inflammation is linked to poor outcomes in sepsis and wound healing, which are multi-phased physiological responses. Eicosanoids, a class of bioactive lipids, play a major regulatory role in these physiologies. In this study, the ablation of the ceramide-1-phosphate (C1P) interaction site in the eicosanoid biosynthetic enzyme, group IVA cytosolic phospholipase A2, in mice (cPLA2a-KI mice) resulted in enhanced and sustained neutrophil infiltration into both wounds and the peritoneum during the inflammatory phase of wound healing and sepsis. Enhanced neutrophil infiltration (i.e., neutrophilia) was associated with significant improvements in wound healing and the survival of mice to sepsis. As neutrophilia at the site of injury or infection normally associates with a poor outcome, our laboratory investigated this Neutrophil Conundrum by characterizing the cPLA2a-KI neutrophils, which showed enhanced N2-subtype markers, trans-endothelial migration, phagocytosis and VEGF with a concomitant decrease in TNFa, neutrophil extracellular trap production, N1-subtype markers, and endothelial cell damage versus wild-type neutrophils. This N2 polarization of cPLA2a-KI neutrophils was due to an induction of the 5-HETE/5-oxo-ETE biosynthetic pathway and activation of the OXER1 receptor. Unbiased proteomics identified perturbations in the pentose phosphate pathway (PPP) specific to OXER1 signaling in the cPLA2a-KI neutrophils, and modulation of the PPP recapitulated specific aspects of the N2 phenotype. Thus, C1P via cPLA2a negatively regulates 5-oxo-ETE biosynthesis, which controls neutrophil polarization via the PPP |
| Institute: | University of South Florida |
| Department: | CAS |
| Laboratory: | Chalfant |
| Last Name: | Maus |
| First Name: | Kenneth |
| Address: | 4202 E Fowler Ave, Tampa, FL, 33620, USA |
| Email: | kmaus@usf.edu |
| Phone: | 8139283137 |
Summary of all studies in project PR001576
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002445 | The interaction of ceramide-1-phosphate with group IVA cytosolic phospholipase A2 modulates neutrophil polarization during inflammatory responses | Mus musculus | University of South Florida | MS | 2023-02-05 | 1 | 32 | Uploaded data (2.7M)* |
