The role of natural IgM in myocardial ischemia-reperfusion injury.
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.
Zhang
Ming
M
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.
Michael
Lloyd H
LH
Grosjean
Sandrine A
SA
Kelly
Ralph A
RA
Carroll
Michael C
MC
Entman
Mark L
ML
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007075:Immunoglobulin M / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D017202:Myocardial Ischemia / Q000276:immunology*; D015428:Myocardial Reperfusion Injury / Q000276:immunology* / Q000473:pathology*; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology; D011951:Receptors, Complement / Q000235:genetics
D018398:Homeodomain Proteins; D007075:Immunoglobulin M; D011951:Receptors, Complement; C064658:RAG-1 protein