Abstract 9912: The Activation of Natural Killer T Cells Ameliorates Myocardial Ischemia Reperfusion Injury in Mice
Background Natural killer T (NKT) cells play an important role in tissue inflammation in various diseases due to the capacity to produce inflammatory cytokines and orchestrate tissue inflammation. It has been reported that preactivation of NKT cells with α-galactosylceramide (α-GC) protects against hepatic ischemia reperfusion injury. However no previous studies have examined the pathophysiological role of NKT cells in myocardial ischemia reperfusion injury.
Methods A 45 minute occlusion of the left coronary artery followed by 24 hours reperfusion (Ischemia/Reperfusion; I/R) or sham operation was performed in male C57BL/6J mice. I/R mice received the single injection of either αGC (100μg/kg body weight, I/R+αGC, n=14), which specifically activates NKT cells, or vehicle (I/R+vehicle, n=16) 30 minutes before reperfusion. Infiltration of inflammatory cells was assessed by immunohistochemical staining and gene expression of inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were quantified by RT-PCR in the left ventricle.
Results Hemodynamics such as heart rate and blood pressure were not affected by αGC. The serum and myocardial gene expression levels of IFN-γ did not differ between sham and I/R+vehicle, and they were significantly increased in I/R+αGC in consistent with the activation of NKT cells. Infarct size was significantly smaller in I/R+αGC than I/R+vehicle (infarct size/area at risk: 37.8±2.7 vs 47.1±2.5 %, P<0.05), with no significant changes in area at risk (area at risk/left ventricle: 58.5±2.3 vs 58.9±2.7 %, P=NS). Serum Troponin-I was also lowered in I/R+αGC (5.8±0.8 vs 8.7±0.7 ng/ml, P<0.05). The number of infiltrating CD3 positive cells was lower in I/R+αGC (13.7±2.6 vs 36.3±7.6 cells/HPF, P<0.05). In parallel, mRNA expression of TNF-α and IL-1β were lower in I/R+αGC compared to I/R+vehicle (relative value of sham+vehicle: TNF-α 5.8±0.9 vs 11.8±1.9, P<0.05 and IL-1β 5.3±1.6 vs 30.0±7.8, P<0.05).
Conclusions The activation of NKT cells ameliorated myocardial ischemia reperfusion injury in mice possibly through the inhibition of inflammatory cell infiltration and inflammatory cytokine expression within the heart.
- © 2011 by American Heart Association, Inc.