Purine excretion by mouse peritoneal macrophages lacking adenosine deaminase activity

T. S. Chan

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)925-929
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume76
Issue number2
StatePublished - 1979
Externally publishedYes

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Adenosine Deaminase
Peritoneal Macrophages
Purine Nucleosides
Macrophages
Erythroblasts
Phagocytosis
Adenosine Deaminase Inhibitors
Pentostatin
Severe Combined Immunodeficiency
Mononuclear Phagocyte System
Erythropoiesis
Uric Acid
Adenosine
Culture Media
Theoretical Models
purine
Lymphocytes
2'-deoxyadenosine

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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abstract = "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.",
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