Extracellular hmgb1 functions as an innate immune-mediator implicated in murine cardiac allograft acute rejection.
Hmgb1, an evolutionarily conserved chromosomal protein, was recently re-discovered to be an innate immune-mediator contributing to both innate and adaptive immune responses. Here, we show a pivotal role for Hmgb1 in acute allograft rejection in a murine cardiac transplantation model. Extracellular Hmgb1 was found to be a potent stimulator for adaptive immune responses. Hmgb1 can be either passively released from damaged cells after organ harvest and ischemia/reperfusion insults, or actively secreted by allograft infiltrated immune cells. After transplantation, allografts show a significant temporal up-regulation of Hmgb1 expression accompanied by inflammatory infiltration, a consequence of graft destruction. These data suggest the involvement of Hmgb1 in acute allograft rejection. In line with these observations, treatment of recipients with rA-box, a specific blockade for endogenous Hmgb1, significantly prolonged cardiac allograft survival as compared to those recipients treated with either rGST or control vehicle. The enhanced graft survival is associated with reduced allograft expression of TNFalpha, IFNgamma and Hmgb1 and impaired Th1 immune response.
Huang
Y
Y
Laboratory of Transplantation, Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yin
H
H
Han
J
J
Huang
B
B
Xu
J
J
Zheng
F
F
Tan
Z
Z
Fang
M
M
Rui
L
L
Chen
D
D
Wang
S
S
Zheng
X
X
Wang
C-Y
CY
Gong
F
F
D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D017931:DNA Primers; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007113:Immunity, Innate; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D017931:DNA Primers; D024243:HMGB1 Protein; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha