TY - JOUR
T1 - Specific Immunosuppressive Effects of Constant Infusion of 2́-Deoxycoformycin
AU - Trotta, Paul P.
AU - Balia, M. Earl
AU - Ikehara, Susumu
AU - Pahwa, Rajendra
AU - Good, Robert A.
AU - Tedde, Antonio
PY - 1981/6/1
Y1 - 1981/6/1
N2 - The effect of continuous infusion into C57BL/6J mice of 2́-deoxycoformycin (DCF), a tight-binding inhibitor of adenosine deaminase, on the biological function of bone marrow stem cells and T- and B-lymphocytes was evaluated. Greater than 85% inhibition of adenosine deaminase in erythrocytes, thymus, and bone marrow was noted after DCF infusion at 0.4 mg per kg body weight per day, while lesser extents of inhibition were characteristic of spleen and lymph nodes. The reconstitution of lethally irradiated C57BL/6J mice with bone marrow cells from DCF- and 0.9% NaCI infused mice of the same strain was compared. The two groups of animals were virtually identical with respect to (a) the number of spleen colony-forming units, (b) the response of splenic lymphocytes to both B- and T-cell mitogens, (c) hematological analysis of peripheral blood elements, and (d) survival time, thus strongly supporting a lack of effect of DCF infusion on the capacity of stem cells to differentiate. In contradistinction, DCF infusion was highly lym-phocytotoxic as noted by the severe necrosis in both B- and T-cell regions in lymph nodes and spleen and by the dramatic weight reduction in spleen and thymus. Histopathology of other tissues including bone marrow was normal except for the occurrence of hepatitis. A striking decrease in blastogenesis induced by the mitogens concanavalin A, phytohemagglutinin, and Escherichia coil lipopolysaccharides was also observed after DCF infusion. Consistent with these data, in vitro incubation of bone marrow cells with DCF did not impair the number of spleen colony-forming units produced in lethally irradiated mice. These data suggest a potential use for adenosine deaminase inhibitors in the prevention of graft-versus-host disease in hematopoietic transplantation.
AB - The effect of continuous infusion into C57BL/6J mice of 2́-deoxycoformycin (DCF), a tight-binding inhibitor of adenosine deaminase, on the biological function of bone marrow stem cells and T- and B-lymphocytes was evaluated. Greater than 85% inhibition of adenosine deaminase in erythrocytes, thymus, and bone marrow was noted after DCF infusion at 0.4 mg per kg body weight per day, while lesser extents of inhibition were characteristic of spleen and lymph nodes. The reconstitution of lethally irradiated C57BL/6J mice with bone marrow cells from DCF- and 0.9% NaCI infused mice of the same strain was compared. The two groups of animals were virtually identical with respect to (a) the number of spleen colony-forming units, (b) the response of splenic lymphocytes to both B- and T-cell mitogens, (c) hematological analysis of peripheral blood elements, and (d) survival time, thus strongly supporting a lack of effect of DCF infusion on the capacity of stem cells to differentiate. In contradistinction, DCF infusion was highly lym-phocytotoxic as noted by the severe necrosis in both B- and T-cell regions in lymph nodes and spleen and by the dramatic weight reduction in spleen and thymus. Histopathology of other tissues including bone marrow was normal except for the occurrence of hepatitis. A striking decrease in blastogenesis induced by the mitogens concanavalin A, phytohemagglutinin, and Escherichia coil lipopolysaccharides was also observed after DCF infusion. Consistent with these data, in vitro incubation of bone marrow cells with DCF did not impair the number of spleen colony-forming units produced in lethally irradiated mice. These data suggest a potential use for adenosine deaminase inhibitors in the prevention of graft-versus-host disease in hematopoietic transplantation.
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M3 - Article
C2 - 6972248
AN - SCOPUS:0019515506
VL - 41
SP - 2189
EP - 2196
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 6
ER -