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Updated: May 5, 2026
Measurement of Antibody Effects on Cellular Function of Isolated Cardiomyocytes
Published on: March 8, 2013
Antibody to CD-18 exerts endothelial and cardiac protective effects in myocardial ischemia and reperfusion
1Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Insights
This study shows that blocking neutrophil adherence with MAbR15.7 antibody protects against heart damage and endothelial dysfunction during myocardial ischemia and reperfusion. This demonstrates a CD18-dependent mechanism in reperfusion injury.
Area of Science:
- Cardiovascular Science
- Immunology
- Cell Biology
Background:
- Myocardial ischemia and reperfusion (MI+R) cause significant heart injury and endothelial dysfunction.
- Neutrophil adherence glycoproteins, like CD18, play a role in inflammatory processes during reperfusion injury.
Purpose of the Study:
- To investigate the effects of MAbR15.7, an antibody targeting CD18, on endothelial dysfunction and myocardial injury in a feline model of MI+R.
- To elucidate the role of CD18-dependent neutrophil adherence in reperfusion injury.
Main Methods:
- Cats underwent 1.5 hours of coronary artery occlusion followed by 4.5 hours of reperfusion.
- MAbR15.7 antibody was administered to assess its protective effects.
- Measurements included plasma creatine kinase (CK) activity, myocardial necrosis, myeloperoxidase (MPO) activity, and coronary ring vasoreactivity to acetylcholine (ACh) and A-23187.
Main Results:
- MI+R led to elevated CK, myocardial necrosis, high MPO activity, and impaired vasodilation.
- MAbR15.7 treatment significantly reduced CK levels, myocardial necrosis (2% vs. 30.8%), and MPO activity.
- Coronary rings from MAbR15.7-treated cats showed preserved responses to ACh and A-23187.
Conclusions:
- Myocardial ischemia and reperfusion involve a CD18-dependent neutrophil adherence mechanism contributing to injury and endothelial dysfunction.
- Inhibiting neutrophil adherence with MAbR15.7 provides significant protection against reperfusion injury in this model.
Abstract:
We studied the effects of MAbR15.7, an antibody directed against the common beta-chain (CD-18) of a family of neutrophil adherence glycoproteins, on endothelial dysfunction and myocardial injury in a model of myocardial ischemia and reperfusion in cats. Pentobarbital-anesthetized cats were subjected to 1.5 h occlusion of the left anterior descending coronary artery (LAD) and 4.5 h of reperfusion. MI + R resulted in severe myocardial injury and endothelial dysfunction, including significant elevation of plasma creatine kinase (CK) activity, marked myocardial necrosis, high cardiac myeloperoxidase (MPO) activity in ischemic cardiac tissue, and loss of response of LAD coronary rings to the endothelium-dependent vasodilators, acetylcholine (ACh) and A-23187. In contrast, MAbR15.7-treated cats exhibited a lower plasma CK activity at every time point observed after 2 h, a reduced area of cardiac necrosis (2 +/- 1 vs. 30.8 +/- 2.5% of area-at-risk, P less than 0.001), lower MPO activity in the ischemic region (P less than 0.01), and significantly preserved vasorelaxant responses of LAD coronary rings to endothelium-dependent vasodilators, ACh (P less than 0.001), and A-23187 (P less than 0.001). These results indicate that myocardial ischemia and reperfusion induces significant myocardial injury and endothelial dysfunction in the cat involving a CD18-dependent neutrophil adherence mechanism. Inhibition of neutrophil adherence to the endothelium exerts significant protective effects in this model of reperfusion injury.
