Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury

Area of Science:

• Immunology
• Cardiovascular Biology
• Complement System

Background:

• The complement system is crucial for innate and adaptive immunity, with three activation pathways: classical, alternative, and lectin.
• While the complement system's role in ischemia-reperfusion injury is known, the specific involvement of the lectin pathway remains unclear.

Purpose of the Study:

• To investigate the role of the lectin complement pathway in myocardial ischemia-reperfusion injury.
• To evaluate the therapeutic potential of blocking the lectin pathway in a rat model of heart attack.

Main Methods:

• Monoclonal antibodies (mAbs) were generated against rat mannose-binding lectin (rMBL).
• The inhibitory capacity of mAbs was assessed in vitro and in vivo using a rat model of myocardial ischemia-reperfusion (coronary artery occlusion followed by reperfusion).
• Measurements included complement C3 deposition, creatine kinase loss, infarct size, neutrophil infiltration, and expression of proinflammatory genes.

Main Results:

• One mAb (P7E4) effectively inhibited the lectin pathway in vitro and in vivo.
• P7E4 treatment significantly reduced complement C3 deposition, myocardial damage (creatine kinase loss, infarct size), and neutrophil infiltration in the heart post-ischemia-reperfusion.
• P7E4 also attenuated the expression of key proinflammatory genes, including intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6.

Conclusions:

• The lectin complement pathway is activated during myocardial ischemia-reperfusion and contributes to tissue injury.
• Blocking the lectin pathway with inhibitory mAbs offers cardioprotection by mitigating neutrophil infiltration and reducing proinflammatory responses.