Delineating the relationships among the formation of reactive oxygen species, cell membrane instability and innate autoimmunity in intestinal reperfusion injury

作者：Lee Haekyung; Ko Eun Hee; Lai Mark; Wei Na; Balroop Javi; Kashem Zerin; Zhang Ming^*

来源：Molecular Immunology, 2014, 58(2): 151-159.

DOI：10.1016/j.molimm.2013.11.012

• Reactive oxygen species
• Cell membrane instability
• Natural IgM
• Complement
• Reperfusion injury
• Trehalose

Acute intestinal ischemia is a medical emergency with a high mortality rate, attesting to the need for a better understanding of its pathogenesis and the development of effective therapies. The goal of this study was to delineate the relationships among intracellular and extracellular events in intestinal ischemia/reperfusion (I/R) injury, particularly the formation of reactive oxygen species (ROS), cell membrane instability associated with lipid peroxidation and the innate autoimmune response mediated by natural IgM and complement. A murine model of natural IgM-mediated intestinal I/R was used. Mice overexpressing anti-oxidant enzyme SOD1 were found to have significantly reduced intestinal tissue damage and complete blockage of IgM-mediated complement activation compared with WT controls. To determine if cell membrane instability was an event intermediate between ROS formation and natural IgM-mediated innate autoimmune response, the cell membrane stabilizer (trehalose) was administered to WT mice prior to the induction of intestinal ischemia. Treatment with trehalose significantly protected animals from I/R injury and inhibited IgM-mediated complement activation although it did not prevent membrane lipid peroxidation. These data indicate that in normal mice subjected to I/R injury, intracellular ROS formation is an event upstream of the lipid peroxidation which results in cell membrane instability. The membrane instability leads to an innate autoimmune response by natural IgM and complement. Trehalose, a nontoxic disaccharide tolerated well by animals and humans, has promise as a protective agent for patients with medical conditions related to acute intestinal ischemia.

• 出版日期2014-4