Published online before print June 7, 2007

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(American Journal of Pathology. 2007;171:507-512.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.061042

Tissue-Specific Effects of the Nuclear Factor B Subunit p50 on Myocardial Ischemia-Reperfusion Injury

Stefan Frantz^*, Jochen Tillmanns^*, Peter J. Kuhlencordt^*, Isabel Schmidt^*, Anna Adamek^*, Charlotte Dienesch^*, Thomas Thum^*, Steve Gerondakis, Georg Ertl^* and Johann Bauersachs^*

From the Medizinische Klinik und Poliklinik I,^* Herz-/Kreislaufzentrum, Universität Würzburg,Würzburg, Germany, and The Walter and Eliza Hall Institute of Medical Research, Parcville, Victoria, Australia

Nuclear factor B (NF-B) is a ubiquitous transcription factor activated by various stimuli implicated in ischemia-reperfusion injury. However, the role of NF-B in cardiac ischemia-reperfusion injury has not yet been well defined. Therefore, we investigated reperfusion damage in mice with targeted deletion of the NF-B subunit p50. Electrophoretic mobility shift assays validated NF-B activation in wild-type (WT) but not 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 with matching WT mice. Although adhesion molecules such as intercellular adhesion molecule were up-regulated in left ventricles of p50 KO animals, 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. Thus, deletion of the NF-B subunit p50 reduces ischemia-reperfusion injury in vivo, associated with less neutrophil infiltration. Bone marrow transplantation experiments indicate that impaired NF-B activation in p50 KO leukocytes attenuates cardiac damage.

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