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Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice
A J Palazzo1, S P Jones, W G Girod
1Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3392, USA.
Abstract:
Previous studies have demonstrated that circulating neutrophils (PMNs) contribute to the pathophysiology of myocardial ischemia-reperfusion (MI/R) injury. PMN-endothelial cell interactions are highly regulated by adhesive interactions between PMN CD11/CD18 and coronary endothelial cell intercellular adhesion molecule-1 (ICAM-1). We investigated the effects of MI/R in wild-type, CD18-, and ICAM-1-deficient (-/-) mice. Wild-type (n = 6), CD18 -/- (n = 6), and ICAM-1 -/- (n = 6) mice were subjected to 30 min of myocardial ischemia and 120 min of reperfusion to determine the extent of PMN infiltration and myocardial cell necrosis. Myocardial infarction (% of the area at risk) was 45.1 +/- 5.9 in wild-type mouse hearts. In contrast, the extent of myocardial infarction was significantly (P < 0.05) reduced in the CD18 (19.3 +/- 5.1%)- and ICAM-1 (17.9 +/- 3.2%)-deficient mice. Similarly, PMN infiltration into the ischemic-reperfused myocardium was attenuated by 54% in the CD18 -/- mice and by 32% in ICAM-1 -/- mice compared with wild-type hearts. Deficiency in either CD18 or ICAM-1 expression results in a marked reduction in PMN accumulation and myocardial necrosis after acute MI/R.
Insights
Myocardial ischemia-reperfusion injury is reduced when neutrophils (PMNs) cannot interact with endothelial cells. Deficiencies in CD18 or ICAM-1 significantly decrease PMN infiltration and heart cell damage.
Area of Science:
- Cardiovascular Research
- Immunology
- Cell Biology
Background:
- Circulating neutrophils (PMNs) play a role in myocardial ischemia-reperfusion (MI/R) injury.
- PMN-endothelial cell adhesion is mediated by CD11/CD18 on PMNs and ICAM-1 on endothelial cells.
Purpose of the Study:
- To investigate the role of CD18 and ICAM-1 in MI/R injury.
- To determine the impact of CD18 and ICAM-1 deficiency on PMN infiltration and myocardial necrosis.
Main Methods:
- Myocardial ischemia-reperfusion injury was induced in wild-type, CD18-deficient, and ICAM-1-deficient mice.
- PMN infiltration and myocardial infarction size were quantified.
Main Results:
- Myocardial infarction was significantly reduced in CD18-deficient (19.3%) and ICAM-1-deficient (17.9%) mice compared to wild-type (45.1%).
- PMN infiltration was reduced by 54% in CD18-deficient and 32% in ICAM-1-deficient mice.
Conclusions:
- CD18 and ICAM-1 are critical for PMN infiltration during MI/R injury.
- Targeting CD18-ICAM-1 interactions may reduce myocardial necrosis and improve outcomes after MI/R.