Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin

Busche, Marc N.; Pavlov, Vasile I.; Takahashi, Kazue; Stahl, Gregory L.

doi:10.1152/ajpheart.00049.2009

Cited by 85 publications

(56 citation statements)

References 33 publications

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“…Similar results were obtained in the myocardial model of I/R (MI/R), where the sIgM/MBL KO mice were investigated in an analogous plasma reconstitution mouse model of MI/R (Busche et al, 2009). Echocardiography showed that both MBL and IgM were required for MI/R-induced loss of left ventricular function.…”

Section: Mbl Is a Risk Factor For Tissue Injurysupporting

confidence: 67%

“…During the past decade, in vivo studies of MBL null mice have shown that MBL-deficiency is protective in I/R injuries in heart (Walsh et al, 2005;Busche et al, 2009), kidney (Moller-Kristensen et al, 2005), gut (Hart et al, 2005;Zhang et al, 2006;McMullen et al, 2006), skeletal muscle (Chan et al, 2006) and brain (Cervera et al, 2010;de la Rosa et al, 2014).…”

Section: Mbl Is a Risk Factor For Tissue Injurymentioning

confidence: 99%

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Lessons learned from mice deficient in lectin complement pathway molecules

Genster

Takahashi

Sekine

et al. 2014

Molecular Immunology

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The lectin pathway of the complement system is initiated when the pattern-recognition molecules, mannose-binding lectin (MBL), ficolins or collectin-11, bind to invading pathogens or damaged host cells. This leads to activation of MBL/ficolin/collectin-11 associated serine proteases (MASPs), which in turn activate downstream complement components, ultimately leading to elimination of the pathogen. Mice deficient in the key molecules of lectin pathway of complement have been generated in order to build knowledge of the molecular mechanisms of the lectin pathway in health and disease. Despite differences in the genetic arrangements of murine and human orthologues of lectin pathway molecules, the knockout mice have proven to be valuable models to explore the effect of deficiency states in humans. In addition, new insight and unexpected findings on the diverse roles of lectin pathway molecules in complement activation, pathogen infection, coagulation, host tissue injury and developmental biology have been revealed by in vivo investigations. This review provides an overview of the mice deficient in lectin pathway molecules and highlights some of the most important findings that have resulted from studies of these.

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Section: Mbl Is a Risk Factor For Tissue Injurysupporting

confidence: 67%

Section: Mbl Is a Risk Factor For Tissue Injurymentioning

confidence: 99%

Lessons learned from mice deficient in lectin complement pathway molecules

Genster

Takahashi

Sekine

et al. 2014

Molecular Immunology

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“…Although classical pathway activation cannot be excluded, our findings of increased C4bc is in accordance with lectin pathway activation during the acute phase,33, 42 although the role of the lectin pathway in post‐MI HF is still elusive.…”

Section: Discussionsupporting

confidence: 82%

“…Particularly, the lectin pathway has been linked to complement‐mediated myocardial injury and HF,18, 33, 34, 35 and lectin pathway recognition molecules were therefore thoroughly investigated in the present study. MBL and the ficolins are circulating recognition molecules binding to molecular structures on damaged host cells further activating the mannose‐binding serine proteases, MASP1 and MASP2 36.…”

Section: Discussionmentioning

confidence: 99%

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

et al. 2018

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AimsHeart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction.Methods and resultsThe LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary intervention‐treated ST‐elevation myocardial infarction herein underwent a post hoc analysis. Blood samples were drawn from inclusion to Day 5 and at 42 day follow‐up, and biomarkers were measured with enzyme immunoassays. Regional myocardial contractility was measured by echocardiography as wall motion score index (WMSI). The cardiogenic shock group (n = 9) was compared with the non‐shock group (n = 52). Controls (n = 44) were age‐matched and sex‐matched healthy individuals. C4bc, C3bc, C3bBbP, and sC5b‐9 were elevated in patients at inclusion compared with controls (P < 0.01). The shock group had higher levels compared with the non‐shock group for all activation products except C3bBbP (P < 0.05). At Day 42, all products were higher in the shock group (P < 0.05). In the shock group, sC5b‐9 correlated significantly with WMSI at baseline (r = 0.68; P = 0.045) and at Day 42 (r = 0.84; P = 0.036). Peak sC5b‐9 level correlated strongly with WMSI at Day 42 (r = 0.98; P = 0.005). Circulating endothelial cell activation markers sICAM‐1 and sVCAM‐1 were higher in the shock group during the acute phase (P < 0.01), and their peak levels correlated with sC5b‐9 peak level in the whole HF population (r = 0.32; P = 0.014 and r = 0.30; P = 0.022, respectively).ConclusionsComplement activation discriminated cardiogenic shock from non‐shock in acute ST‐elevation myocardial infarction complicated by HF and correlated with regional contractility and endothelial cell activation, suggesting a pathogenic role of complement in this condition.

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“…Other studies have emphasized the interaction of IgM with MBL resulting in activation of the lectin pathway [16]. Myocardial and gastrointestinal models in MBL knockout mice have shown both IgM and MBL to be essential for generation of tissue damage [17,18]. Studies in rat intestinal I/R and in patients with myocardial infarcts have also suggested a role for CRP in local complement activation [19,20].…”

Section: Introductionmentioning

confidence: 99%

Immunoglobulin M, C-Reactive Protein and Complement Activation in Rat Hepatic Ischemia-Reperfusion Injury

Diepenhorst

Graaf²,

Niessen³

et al. 2014

Eur Surg Res

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Background: Ischemia-reperfusion (I/R) models have shown that C-reactive protein (CRP) and immunoglobulin M (IgM) are involved in complement activation. Binding of CRP and IgM to damaged cell membranes initiates complement activation and aggravates I/R injury in various organs. However, the time course of CRP- and IgM-mediated complement activation and the relation to hepatocellular injury and inflammation in liver I/R are unknown. Aim: To evaluate the time course of IgM- and CRP-related complement activation and the relation to hepatocellular injury and inflammation in a hepatic I/R rat model. Methods: Male Wistar rats were allocated to (1) five groups of animals exposed to 60 min of partial ischemia (70%) induced via clamping of the left segmental portal triad, followed by 0, 3, 6, 12 or 24 h of reperfusion (n = 6 in each group); (2) five groups of sham-operated animals with corresponding reperfusion times (n = 5), and (3) a control group sacrificed before ischemia (n = 5). Hepatocellular injury, inflammatory response, rat plasma CRP and IgM levels and immunohistochemical depositions of CRP, IgM and C3 were assessed for each group. Results: Histopathological injury scores of hematoxylin and eosin sections of ischemic liver lobes demonstrated increasing values throughout the reperfusion time with a peak at 12 h. Plasma aminotransferases (alanine aminotransferase and aspartate aminotransferase) significantly increased after 3 h of reperfusion, peaking at 6 h (3,100 ± 800 U/l; p < 0.05). Hepatic neutrophil influx significantly increased from 3 to 6 h of reperfusion (p < 0.05) and demonstrated the highest value at 12 h (1.1 ± 0.2 U/mg of protein). Plasma IL-6 levels in the ischemia groups showed peak values after 6 h of reperfusion, decreasing significantly thereafter (p < 0.05). Plasma CRP values reached highest levels after 3 h of reperfusion (mean 91 ± 5% of control pool), decreasing significantly thereafter. Rat IgM concentrations in plasma did not significantly change throughout the reperfusion time. Immunohistochemical depositions of IgM, CRP and C3 in ischemic lobes demonstrated a similar pattern in time, reaching maximum values at 12 h of reperfusion. The percentages of depositions of CRP and IgM were significantly correlated [r(S) = 0.569; p < 0.001; Spearman test]. The time course of C3 and CRP depositions throughout reperfusion and C3 and IgM staining were significantly similar [r(S) = 0.797 and r(S) = 0.656, respectively; p < 0.0001; ANOVA]. Conclusions: CRP and IgM depositions demonstrate a parallel time course throughout the reperfusion to hepatocellular damage, inflammatory response and activated complement deposition in this rat hepatic I/R model. Furthermore, the time course of CRP and IgM depositions was significantly similar to that of activated complement depositions.

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Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin

Cited by 85 publications

References 33 publications

Lessons learned from mice deficient in lectin complement pathway molecules

Lessons learned from mice deficient in lectin complement pathway molecules

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

Immunoglobulin M, C-Reactive Protein and Complement Activation in Rat Hepatic Ischemia-Reperfusion Injury

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