PURINE EXCRETION BY MOUSE PERITONEAL MACROPHAGES LACKING ADENOSINE-DEAMINASE ACTIVITY

Deoxyadenosine, a cytotoxic purine nucleoside, is excreted in large amounts by patients with severe combined immunodeficiency disease associated with deficiency of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4). To identify the source of the purine nucleoside, purine excretion by macrophages was studied by using mouse peritoneal macrophages as an experimental model system. Normally, macrophages excrete a large quantity of uric acid into the culture medium. However, in the presence of deoxycoformycin, a potent inhibitor of adenosine deaminase, these macrophages also excreted deoxyadenosine. Furthermore, phagocytosis of nucleated erythrocytes augmented the excretion of deoxyadenosine. Macrophages are involved in the phagocytosis of nuclei that are extruded from normoblasts during erythropoiesis and also of senescent cells in lymphoid organs. A hypothesis is proposed that macrophages of the reticuloendothelial system are a source of deoxyadenosine, which is one of the two cytotoxic purine nucleosides (the other is adenosine) apparently responsible for the suppression of immune functions in patients with adenosine deaminase deficiency.