title: Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin.
abstract: Complement activation has been shown to play an important role in the inflammation and tissue injury following myocardial ischemia and reperfusion (MI/R). Several recent studies from our laboratory demonstrated the importance of mannose-binding lectin (MBL) as the initiation pathway for complement activation and the resulting pathological effects following MI/R. However, other studies from the past suggest an important role of the classical pathway and perhaps natural antibodies. In the present study, we used newly generated genetically modified mice that lack secreted IgM (sIgM), MBL-A, and MBL-C (sIgM/MBL null) in a plasma reconstitution mouse model of MI/R. Following 30 min of ischemia and 4 h of reperfusion, left ventricular ejection fractions were significantly higher in sIgM/MBL null mice reconstituted with MBL null or sIgM/MBL null plasma compared with reconstitution with wild-type (WT) plasma or WT mice reconstituted with WT plasma following MI/R. Serum troponin I concentration, myocardial polymorphonuclear leukocyte infiltration, and C3 deposition were dependent on the combined presence of sIgM and MBL. These results demonstrate that MI/R-induced complement activation, inflammation, and subsequent tissue injury require both IgM and MBL. Thus MBL-dependent activation of the lectin pathway may not be completely antibody independent in I/R models.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Marc N
authors.initials: MN
authors.lastname: Busche
authors.forename: Vasile
authors.initials: V
authors.lastname: Pavlov
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003167:Complement Activation / Q000235:genetics; D003176:Complement C3 / Q000378:metabolism; D004195:Disease Models, Animal; D007075:Immunoglobulin M / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D020556:Neutrophil Infiltration; D010446:Peptide Fragments / Q000097:blood; D013318:Stroke Volume; D019210:Troponin I / Q000097:blood; D014463:Ultrasonography; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D003176:Complement C3; D007075:Immunoglobulin M; D037601:Mannose-Binding Lectin; C445639:Mbl2 protein, mouse; D010446:Peptide Fragments; D019210:Troponin I; C069858:mannose binding protein A; C061291:troponin I (104-115)