A canine model of induced purine nucleoside phosphorylase deficiency.
Purine nucleoside phosphorylase (NP EC 2.4.2.1) deficiency in man is associated with selective T cell dysfunction and normal B cell immunity. To create an in-vivo model of this immune deficiency, we administered 8-aminoguanosine to dogs. This water soluble nucleoside was rapidly converted by NP to the more potent product inhibitor 8-aminoguanine, which had a Ki of 0.52 microM. The accumulation of inosine and exogenous deoxyguanosine in plasma provided evidence that administration of 8-aminoguanosine was effectively inhibiting NP activity. Four dogs given 8-aminoguanosine and deoxyguanosine concurrently for 5 consecutive days showed mean reductions in peripheral blood lymphocytes of 65 +/- 9% range (55-75%) over the test period. Granulocytes, red blood cells, and plateletes remained within the normal range. Administration of 8-aminoguanosine to dogs provides a model of NP deficiency that will permit studies of the specific control of lymphopoiesis and in-vivo immune function.
D000818:Animals; D001772:Blood Cell Count; D003849:Deoxyguanosine; D004195:Disease Models, Animal; D004285:Dogs; D004912:Erythrocytes / Q000201:enzymology; D006151:Guanosine / Q000031:analogs & derivatives; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced* / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology; D010770:Phosphotransferases / Q000097:blood
D006151:Guanosine; C032533:8-aminoguanosine; D010770:Phosphotransferases; C021892:nucleoside phosphotransferase; D003849:Deoxyguanosine