Fig. 8. Schematic representation of the proposed model of the C1P-cPLA₂α interaction modulating neutrophil polarization.

cPLA₂α not bound to C1P increases 5-HETE and 5-oxo-ETE production and paracrine and autocrine signaling through OXER1, resulting in activation of the MAPK pathway and downstream suppression of the PPP. This lipid profile correlates with decreased endothelial damage (Syndecan-1), NETosis, ROS production, and TNF production and increased neutrophil phagocytosis, VEGF production, and NTEM. Alternatively, C1P recruits cPLA₂α to the Golgi apparatus and increases COX-2–derived eicosanoids (PGE₂ and PDE₂), decreases 5-HETE and 5-oxo-ETE biosynthesis, and results in pro-inflammatory neutrophil behaviors.