Objective: Nuclear factor kappa B (NF-kB) is a ubiquitous transcription factor activated by various stimuli implicated in ischemia reperfusion injury. However, the role of NF-kB in cardiac ischemia-reperfusion injury has not yet been well defined. Therefore, we investigated reperfusion damage in mice with targeted deletion of the NF-kB subunit p50.

Methods and results: Electromobility gel shift assays validated NF-kB activation in wild-type (WT), but not in p50 knockout (KO) mice. KO and WT animals underwent 30 minutes of coronary artery ligation and 24 hours of reperfusion in vivo. Ischemia-reperfusion damage was significantly reduced in the p50 KO when compared to matching WT mice. Fewer neutrophils infiltrated the infarct area, suggesting leukocytes as a potential mediator of the protection observed in the p50 KO. This was confirmed in adoptive transfer experiments: Whereas transplantation of KO bone marrow in KO animals sustained the protective effect on ischemia-reperfusion injury, transplantation of WT bone marrow in KO animals abolished it.

Conclusion: Deletion of the NF-kB subunit p50 reduces ischemia- reperfusion injury in vivo associated with less neutrophil infiltration. Bone marrow transplantation experiments indicate that impaired NF-kB activation in p50 KO leukocytes attenuates cardiac damage.