Intestinal ischemia/reperfusion-induced lipid alterations do not correlated with damage or PGE2 production (90.12)

Abstract

Ischemia/reperfusion (IR)-induced injury results in severe tissue damage and causes up to 30,000 human deaths per year in the US. In a mouse model of intestinal IR, C57Bl/6 mice experience significant intestinal damage; however Rag-1-/- mice, which are antibody deficient, do not sustain significant damage. Complement activation is also critical as indicated by the lack of damage in complement receptor 2 deficient (CR2-/-) mice. Additionally, when Rag-1-/- or CR2-/- mice are pretreated with C57Bl/6 antibodies or specific anti-phospholipid monoclonal antibodies, damage is restored to C57Bl/6 levels. We hypothesized that antibodies recognize a specific lipid antigen produced during IR. After subjecting C57Bl/6, CR2-/- and Rag-1-/- mice to either Sham or intestinal ischemia followed by reperfusion, we determined jejunal prostaglandin E2 (PGE2) production and lipid profile. Mass spectrometry analysis of extracted lipids indicated that lysolipids and arachidonic acid (AA) levels increased by 15 min post-ischemia in C57Bl/6 mice. Differences in lysolipids or AA will be detected between C57Bl/6, CR2-/- and Rag-1-/- mice. C57Bl/6 mice produced significantly more Cox-2 mRNA and PGE2 than either CR2-/- or Rag-1-/- mice. Pretreating Rag-1-/- mice with antibodies purified from C57Bl/6 mice restored IR-induced PGE2 production to C57Bl/6 levels. We conclude that antibodies do not influence lipid metabolism, but are required for activation of Cox-2 and subsequent production of PGE2.