Nothing but natural: targeting natural IgM in ischaemia/reperfusion injury

Abstract

This editorial refers to ‘Blockade of self-reactive IgM significantly reduces injury in a murine model of acute myocardial infarction’ by M.S. Haas et al. , doi:10.1093/cvr/cvq141 Ischaemic heart disease and stroke are major causes of morbidity and mortality in the western world. In both clinical entities, reperfusion within several hours is the only established therapy to limit infarct size. However, therapeutic or spontaneous reperfusion itself may contribute to tissue injury. Reoxygenation often aggravates hypoxic cellular changes including mitochondrial alterations, reactive oxygen species generation, intracellular ion imbalance, and damage of membrane constituents. Furthermore, ischaemia induces a sterile inflammatory response, which mainly involves innate immune cells, especially neutrophils.1,2 With the seminal finding that so-called natural antibodies can recognize self-antigens during ischaemia,3 Michael Carroll's group introduced the model of ‘innate autoimmunity’ for ischaemia/reperfusion injury. This concept integrates mechanisms of both intrinsic ischaemic cell injury and initiation of an extrinsic innate immune response.4 According to their hypothesis, ischaemia/reperfusion induces intracellular damage, rendering cells susceptible to a second phase of injury that is initiated by natural antibody-mediated complement activation. Early evidence for the involvement of the complement system in ischaemia/reperfusion injury came from a study from Weisman … *Corresponding author. Tel: +49 931 201 43542; fax: +49 931 201 61633, Email: frantz_s{at}medizin.uni-wuerzburg.de