Zhang, M. et al. The role of natural IgM in myocardial ischemia-reperfusion injury. J. Mol. Cell. Cardiol. 41, 62-67

The CBR Institute for Biomedical Research, Inc., Harvard Medical School, Boston, MA 02115, and Section of Cardiovascular Sciences, The Methodist Hospital, Houston, TX 77030, USA.
Journal of Molecular and Cellular Cardiology (Impact Factor: 4.66). 08/2006; 41(1):62-7. DOI: 10.1016/j.yjmcc.2006.02.006
Source: PubMed


Myocardial ischemia-reperfusion injury represents a combination of factors, namely the intrinsic cellular response to ischemia and the extrinsic acute inflammatory response. Recent studies in mesenteric and skeletal muscle reperfusion models identified natural IgM as a major initiator of pathology through the activation of the complement system and inflammatory cells. To determine whether a similar mechanism is involved in myocardial tissues, mice bearing an altered natural IgM repertoire (Cr2-/-) were examined in a murine model of coronary artery ischemia. Notably, these mice were significantly protected based on the reduced infarct size, limited apoptosis of cardiomyocytes, and decreased neutrophil infiltration. Protection was IgM-dependent as reconstitution of these mice with wild-type IgM restored myocardial reperfusion injury. These results support a model in which natural IgM initiates the acute inflammatory response in the myocardium following ischemia and reperfusion.

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Available from: Mark L Entman, Jan 28, 2014
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    01/2013; 3(1):1. DOI:10.1186/2045-9912-3-1
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    • "Carroll and co-workers28,29 have demonstrated that selective depletion of natural IgM is sufficient to abrogate most ischaemic–reperfusion injury in both murine hindlimb28 or murine intestinal29 reperfusion injury models. The self-target for this monoclonal natural IgM is non-muscle myosin heavy chain type II A and C.30 These data could also be reproduced for the heart.31 Mice baring an altered natural IgM repertoire (Cr2−/−) were protected from ischaemia/reperfusion injury and had a reduction in inflammatory infiltrates. "
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    • "The results obtained by studying plasma of septic patients suggest that complement amplification may be stimulated at the onset of SIRS not only by extra C3b from classical and lectin complement pathway (Windbichler et al., 2004; Zhang et al., 2006), but in addition by the mechanism described here. This mechanism is most likely initiated by released elastase, generating F(ab ) 2 fragments from endogenous IgG molecules. "
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