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http://purl.uniprot.org/citations/11560858http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Complement consists of a complex cascade of proteins involved in innate and adaptive immunity. The cascade can be activated through 3 distinct mechanisms, designated the classical, alternative, and lectin pathways. Although complement is widely accepted as participating in the pathophysiology of ischemia-reperfusion injury, the specific role of the lectin pathway has not been addressed.

Methods and results

Monoclonal antibodies (mAbs; P7E4 and 14C3.74, IgG1kappa isotypes) were raised against rat mannose-binding lectin (rMBL). Both mAbs recognized rMBL-A by Western analysis or surface plasmon resonance. P7E4, but not 14C3.74, exhibited a concentration-dependent inhibition of the lectin pathway, with maximal effect at 10 microg/mL. In vivo, rats were subjected to 30 minutes of left coronary artery occlusion and 4 hours of reperfusion. Complement C3 deposition was greatly attenuated in hearts pretreated with P7E4 compared with 14C3.74-treated hearts. Pretreatment with P7E4 (1 mg/kg) significantly reduced myocardial creatine kinase loss (48%), infarct size (39%), and neutrophil infiltration (47%) compared with 14C3.74-treated animals. In addition, P7E4 pretreatment significantly attenuated the expression of proinflammatory genes (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6) after ischemia-reperfusion.

Conclusions

The lectin complement pathway is activated after myocardial ischemia-reperfusion and leads to tissue injury. Blockade of the lectin pathway with inhibitory mAbs protects the heart from ischemia-reperfusion by reducing neutrophil infiltration and attenuating proinflammatory gene expression."xsd:string
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http://purl.uniprot.org/citations/11560858http://purl.uniprot.org/core/author"Stahl G.L."xsd:string
http://purl.uniprot.org/citations/11560858http://purl.uniprot.org/core/author"Montalto M.C."xsd:string
http://purl.uniprot.org/citations/11560858http://purl.uniprot.org/core/author"Jordan J.E."xsd:string
http://purl.uniprot.org/citations/11560858http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11560858http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/11560858http://purl.uniprot.org/core/pages"1413-1418"xsd:string
http://purl.uniprot.org/citations/11560858http://purl.uniprot.org/core/title"Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury."xsd:string
http://purl.uniprot.org/citations/11560858http://purl.uniprot.org/core/volume"104"xsd:string
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