RGD Reference Report - Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury. - Rat Genome Database

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Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury.

Authors: Jordan, JE  Montalto, MC  Stahl, GL 
Citation: Jordan JE, etal., Circulation. 2001 Sep 18;104(12):1413-8.
RGD ID: 1582136
Pubmed: PMID:11560858   (View Abstract at PubMed)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
C3RatMyocardial Reperfusion Injury  IEP protein:increased expression:myocardiumRGD 
C3HumanMyocardial Reperfusion Injury  ISOC3 (Rattus norvegicus)protein:increased expression:myocardiumRGD 
C3MouseMyocardial Reperfusion Injury  ISOC3 (Rattus norvegicus)protein:increased expression:myocardiumRGD 
Mbl1RatMyocardial Reperfusion Injury  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
C3  (complement C3)
Mbl1  (mannose binding lectin 1)

Genes (Mus musculus)
C3  (complement component 3)

Genes (Homo sapiens)
C3  (complement C3)


Additional Information