Comparison Log
2024-12-01 05:28:29.493033
mwtab Python Library Version: 1.2.5
Source:      https://www.metabolomicsworkbench.org/rest/study/analysis_id/AN003983/mwtab/...
Study ID:    ST002445
Analysis ID: AN003983
Status:      Inconsistent

Sections "PROJECT" contain missmatched items: {('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'), ('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')}