In vivo immunosuppressive effect and the decreasing expression of MHC class II antigens by purine nucleoside phosphorylase inhibitor 8-amino-9-benzylguanine in recipient tissues of canine renal allograft rejection.
8-Amino-9-benzylguanine (8-ABG), a potent purine nucleoside phosphorylase inhibitor, was administered to dogs for 10 days following single renal transplantation. A significant prolongation of graft survival was observed in the groups treated with 100 and 150 mg kg/day of 8-ABG per os compared with the control group that was not treated with any immunosuppressant. Expression of major histocompatibility complex (MHC) class II antigens (Ag) was investigated in the normal kidney(s) and renal allografts of mongrel dogs after single renal transplantation. The 8-ABG was administered to the normal and renal allografted dogs and no detectable MHC class II Ag in the normal kidneys was found. During acute rejection, the MHC class II Ag was expressed on the renal tubular epithelium and glomerular vascular endothelium in graft kidneys. The intensity of the MHC class II Ag expression was correlated to the severity of rejection. This abnormal expression of MHC class II Ag on allograft kidney was suppressed by 8-ABG treatment. Our results suggest that MHC class II Ag expression can be induced on the renal allografts during acute rejection. This abnormal expression of MHC class II Ag may serve as a specific index for diagnosis of kidney allograft rejection. That 8-ABG can suppress abnormal expression of MHC class Ag on allografted kidney and prolong graft survival indicates that 8-ABG may provide an alternative approach for the development of a potential new immunosuppressant.
Yen
C Y
CY
Department of Surgery, 804 Military General Hospital, National Defense Medical Center, Taiwan, Republic of China.
Lin
C Y
CY
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000502:physiology; D007678:Kidney Glomerulus / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000276:immunology; D008297:Male; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; C047715:8-amino-9-benzylguanine; D006147:Guanine; D010430:Pentosyltransferases; C067995:nucleoside phosphorylase