Bioluminescence imaging visualizes activation of nuclear factor-kappaB in mouse cardiac transplantation.
BACKGROUND
The purpose of the current study was to evaluate the role of bioluminescence imaging (BLI) in the determination of nuclear factor (NF)-kappaB activation in cardiac allograft rejection and ischemia-reperfusion injury.


METHODS
To visualize NF-kappaB activation, luciferase transgenic mice under the control of a mouse NF-kappaB promoter (NF-kappaB-Luc) were used as donors or recipients of cardiac grafts. Alternatively, NF-kappaB-Luc spleen cells were adoptively transferred into Rag2 -/- mice with or without cardiac allografts. BLI was performed posttransplantation to detect luciferase activity that represents NF-kappaB activation.


RESULTS
The results show that luciferase activity was significantly increased in the cardiac allografts when NF-kappaB-Luc mice were used as recipients as well as donors. Luciferase activity was also elevated in the wild-type cardiac allografts in Rag2 -/- mice that were transferred with NF-kappaB-Luc spleen cells. CD154 monoclonal antibody (mAb) therapy inhibited luciferase activity and induced long-term survival of cardiac allografts. toll-like receptor-9 ligand, CpG DNA, enhanced luciferase activity and abrogated tolerance induction by CD154 mAb. Luciferase activity was also increased in ischemia-reperfusion injury of the cardiac grafts.


CONCLUSIONS
BLI using Luc-NF-kappaB mice is a noninvasive approach to visualize the activation of NF-kappaB signaling in mouse cardiac allograft rejection and ischemia-reperfusion injury. CD154 mAb can inhibit NF-kappaB activation, which is reversed by toll-like receptor engagement.
Ma
Lianli
L
Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Xiang
Zhidan
Z
Sherrill
Taylor P
TP
Wang
Lei
L
Blackwell
Timothy S
TS
Williams
Philip
P
Chong
Anita
A
Chari
Ravi
R
Yin
Deng Ping
DP
D019264:Adoptive Transfer; D000818:Animals; D016027:Heart Transplantation / Q000276:immunology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D049449:Luminescence; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000502:physiology*; D013154:Spleen / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D016328:NF-kappa B; D008156:Luciferases