The role of mesenteric lymph exosomal lipid mediators following intestinal ischemia-reperfusion injury on activation of inflammation

Background Intestinal ischemia caused by hemorrhagic shock is known to induce systemic inflammatory responses. Previous studies have shown that mesenteric lymph (ML) plays a crucial role in gut-mediated inflammation. Lipid mediators, such as lysophosphatidylcholines (LPCs) which contain polyunsaturated fatty acids (PUFAs), are present in the post-shock ML. Exosomes are also present in the ML and act as transcellular carriers of lipids; however, their role in post-shock systemic inflammation has not been revealed. Here, we aimed to identify changes in lipid mediators in ML exosomes after intestinal ischemia. Methods Male Sprague-Dawley rats underwent laparotomy, followed by ML duct cannulation. Animals were subjected to 60 min of intestinal ischemia by superior mesenteric artery clamping, followed by 120 min of reperfusion. ML was obtained before and after intestinal ischemia and exosomes were isolated from ML by ultracentrifugation. The biological activity of ML exosomes was determined using the monocyte NF-κB activation assay. Lipids of ML exosomes were extracted and quantified by liquid chromatography/electrospray ionization mass spectrometry. Results ML exosomes-induced NF-κB activation significantly increased after intestinal ischemia and lipid analysis revealed a significant increase in the concentration of PUFA-containing LPCs. Additionally, PUFA-containing LPCs also induced NF-κB activation. Conclusion Our results suggest that biologically active lipid mediators in ML exosomes may be involved in the inflammatory response after intestinal ischemia. Level of evidence Not applicable (Basic Science paper).