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The role of adenosine in the control of immune function

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Ricerca in clinica e in laboratorio

Summary

In the past several years the study of primary immunodeficiencies has led to an explosive growth of basic information on the pathophysiology of the immune system. In 1972 a deficiency of adenosine deaminase (ADA) was described in two patients with severe combined immunodeficiency (SCID). Shortly thereafter, deficiencies of other enzymes involved in the purine salvage pathway (i.e., purine nucleoside phosphorylase and ecto-5′-nucleotidase) were described in association, respectively, with defective T- and B-lymphocyte activity. Although the exact biochemical mechanism(s) in these immunodeficiencies is not known, elevated levels of adenosine, 2-deoxyadenosine and their metabolites occur in these patients. Adenosine inhibitsin vitro lymphocyte proliferation, T-lymphocyte-mediated cytolysis, monocyte chemotaxis and basophil histamine release. We have found that adenosine increases lymphocyte cAMP levels, by interacting with a specific plasma membrane receptor which leads to the activation of adenylate cyclase. We have also explored the influence of adenosine in the control of histamine release from human basophils and have shown that adenosine inhibits the IgE-mediated release reaction. The action of adenosine on basophils also appears to be mediated by a specific cell-surface receptor. Adenosine also plays a central and complex role in the control of transmethylation reactions. These reactions modulate several immune and inflammatory reactions, including monocyte chemotaxis, lymphocyte mitogenesis, T-lymphocyte-mediated cytolysis, and probably the IgE-mediated release of histamine from basophils. Thus, adenosine may act as an endogenous modulator of immune function by two separate but interrelated effects: its ability to interact with a cell-surface adenosine receptor, and/or to influence intracellular methylation.

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Abbreviations

ADA:

adenosine deaminase

AdoHcy:

S-adenosyl-L-homocysteine

AdoMet:

S-adenosyl-L-methionine

cAMP:

adenosine 3′,5′-monophosphate

EHNA:

erythro9-(2-hydroxy-3-nonyl)-adenine

HCTL:

L-homocysteine thiolactone

SCID:

severe combined immunodeficiency

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Authors and Affiliations

  1. The Johns Hopkins University School of Medicine Clinical Immunology Division, Baltimore, Md

    Gianni Marone, Marshall Plaut & Lawrence M. Lichtenstein

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  1. Gianni Marone
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  2. Marshall Plaut
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  3. Lawrence M. Lichtenstein
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Additional information

This work was supported in part by grants HL 14153 from the Heart and Lung Institute, AI 07290 from the Institutes of Allergy and Infectious Disease, National Institutes of Health (Bethesda, Md) and from theConsiglio Nazionale dette Ricerche (CNR), Roma, Italy, grant no. 79.02392.65.

This is publication # 387, O’Neill Research Laboratories, The Good Samaritan Hospital, 5601 Loch Raven Boulevard, Baltimore, Md 21239.

Recipient of RCDA AI 00231 from the National Institutes of Health, Bethesda, Md.

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Marone, G., Plaut, M. & Lichtenstein, L.M. The role of adenosine in the control of immune function. La Ricerca Clin. Lab. 10, 303–312 (1980). https://doi.org/10.1007/BF02905345

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