Purine metabolic enzymes in lymphocytes. II. Adenosine deaminase and purine nucleoside phosphorylase activities in the immune response.

Purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) activities examined cytochemically in unfixed lymphocytes of patients with lymphoproliferative disorders

Purine Nucleoside Phosphorylase (PNP) and Adenosine Deaminase (ADA) Activities Examined Cytochemically in Unfixed Lymphocytes of Patients With Lymphoproliferative Disorders

The distribution of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in lymphoid organs and lymphocyte subpopulations in mice, and the effect of phytohemagglutinin P (PHA-P) and concanavalin A (Con A) on the enzyme activities were studied. ADA activity was distributed equally in cells from all organs used and no mouse strain differences were observed. In contrast, PNP activity varied with the mouse strain, being highest in C57BL/6 mice and lowest in BALB/c mice, and with the organ in ICR mice, being high in peripheral blood lymphocytes and spleen lymphocytes, low in mesenteric lymph node cells and absent or very weak in thymus cells. T and B lymphocytes were prepared from spleen of ICR mice. High ADA activity was found in both T and B lymphocytes, whereas PNP activity in the T lymphocytes was about one-third of that in the B lymphocytes. PNP activity in thymus cells was increased to the normal level of T lymphocytes in the spleens by cultivation without stimulant. The development of PNP activity in thymus cells was partially inhibited by Con A but was not affected by PHA-P. ADA activity in thymus cells was enhanced by in vitro stimulation with PHA-P but not with Con A. In contrast, in spleen lymphocytes the development of ADA activity was enhanced by stimulation with PHA-P and Con A, and that of PNP activity was enhanced by PHA-P but not by Con A.

The correlation of adenosine deaminase and purine nucleoside phosphorylase activities in human lymphocytes subpopulations and in various lymphoid malignancies

Purine nucleoside metabolizing enzyme activities in mouse thymocytes at different stages of differentiation and maturation

Deficiency of adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) in man is associated with defects of cell-mediated immunity. In horse and cattle ADA activity is virtually absent from erythrocytes1,2. A low activity of PNP was reported for bovine erythrocytes3. If ADA and PNP activities in lymphocytes from horse and cattle are also low, these cells might provide suitable animal models for studying the metabolic disturbances caused by deficiency of ADA or PNP. Therefore we measured the activities of ADA and PNP in erythrocytes and lymphocytes of horse, cattle and man. Previously we reported large differences between erythrocytes of ten mammalian species in activities of several other enzymes of purine and pyrimidine metabolism4,5. We have now found large variations between man, horse and cattle in ADA and PNP activities of erythrocytes and lymphocytes. The ADA activity in horse lymphocytes is low and comparable to that in lymphocytes of patients with severe combined immunodeficiency. Since several lines of evidence6–9 suggest that ADA and PNP deficiency lead to interference with pyrimidine metabolism, we tried to evaluate the relative contributions of de novo synthesis and the salvage pathway to the synthesis of pyrimidine nucleotides in lymphocytes of man and horse. The ratio of activities of orotidylate decarboxylase and uridine kinase in lymphocytes showed a large difference between these two species.

Levels of some purine metabolizing enzymes in lymphocytes from patients with Down's syndrome.

Elevated Adenosine Deaminase and Purine Nucleoside Phosphorylase Activity in Peripheral Blood Null Lymphocytes From Patients With Acquired Immune Deficiency Syndrome

Activities of purine-metabolizing enzymes in human colon carcinoma cell lines and xenograft tumors

Activities of adenosine deaminase and purine nucleoside phosphorylase were determined in thymocytes and splenocytes of rats of 0-423 days old. Activity of adenosine deaminase per cell is highest in newborn rats and decreases with postnatal development, while in splenocytes adenosine deaminase activity increases. No significant age-dependency is found with purine nucleoside phosphorylase in thymocytes and splenocytes. During whole life adenosine deaminase activity is higher in thymocytes and purine nucleoside phosphorylase activity is higher in splenocytes. With thymocytes, adenosine deaminase activity was higher with deoxyadenosine than with adenosine. The Km values of both nucleosides were comparable in 3- and 40-day-old rats.

Erythrocyte adenosine deaminase and purine nucleoside phosphorylase activity in gout

The purine metabolic enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'nucleotidase (5NT) play an important role in normal lymphocyte differentiation. Abnormal levels of one or all of these enzymes have been associated with immunodeficiency diseases and lymphoproliferative disorders. ADA, PNP, and 5NT activity was measured in peripheral blood T cells from 24 patients with Hodgkin disease (HD) (12 in complete remission and 12 with active disease) to determine whether an association existed between enzyme abnormalities and the decreased cellular immune function previously described in this disorder. HD patients had a significantly decreased absolute lymphocyte count (1,618 +/- 1107/mm3; mean +/- SD) compared to controls (2,320 +/- 980; p less than .001). ADA, PNP, and NT activity was assessed in lymphocyte extracts by measuring the conversion of radiolabeled substrates to products over time. ADA activity expressed as mean +/- SEM nanomoles/10(6) lymphocytes/hr was significantly decreased in T cells from HD patients (84.6 +/- 7.5) compared to controls (128 +/- 12.3; p less than 0.025). Likewise, 5NT was significantly decreased in HD patients (12.7 +/- 1.3) compared to controls (24.0 +/- 3.6; p less than .005). There was not a significant difference in PNP activity between both groups. Low 5NT activity was present irrespective of whether patients had active disease (12.1 +/- 1.5) or were in unmaintained complete remission (14.5 +/- 2.4). These findings suggest that biochemical abnormalities may be responsible for or related to the persistent abnormalities in T-cell function noted throughout the clinical course of HD.

Adenosine deaminase and purine nucleoside phosphorylase activity in spleen cells of aged mice

Activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) on undernourished and renourished rats’ thymus

Adenosine Deaminase and Purine Phosphorylase Activities in Lymphocytes and Red Blood Cells of Patients with Carcinoma of the Larynx