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Citations to this article

Effect of adenosine deaminase inhibition upon human lymphocyte blastogenesis.
D A Carson, J E Seegmiller
D A Carson, J E Seegmiller
Published February 1, 1976
Citation Information: J Clin Invest. 1976;57(2):274-282. https://doi.org/10.1172/JCI108278.
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Research Article

Effect of adenosine deaminase inhibition upon human lymphocyte blastogenesis.

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Abstract

The biochemical mechanisms by which a genetically determined deficiency of adenosine deaminase leads to immunodeficiency are still poorly understood and prompted this study. We have examined the effects of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA) upon the response of human peripheral blood mononuclear cells to the mitogen concanavalin A (Con A). Cells isolated from normal volunteers were incubated in microtiter plates in the presence of various inhibitors, and the incorporation of tritrated thymidine or leucine into macromolecular material was measured after 64 h. EHNA at a concentration of 0.3 muM, which inhibited 90% of the adenosine deaminase (ADA) activity in a mononuclear preparation, impaired the incorporation of tritrated leucine into protein; 100 muM EHNA was the minimal concentration that inhibited thymidine uptake. The addition of 15 muM adenosine or 10 muM cyclic AMP to Con A-stimulated lymphocytes inhibited leucine uptake, while millimolar concentrations were required to inhibit thymidine uptake. Lower doses of adenosine and cyclic AMP stimulated thymidine incorporation. The inhibition of thymidine uptake observed with millimolar concentrations of adenosine was independent of the type of mitogen (pokeweed or Con A), the concentration of mitogen, or the medium used, but could be increased if the cells were cultured in a serum with reduced levels of adenosine deaminase. Washout experiments failed to demonstrate a critical period early in immune induction during which adenosine exerted its inhibitory effects. Noninhibitory doses of EHNA potentiated the effects of adenosine and cyclic AMP on leucine and thymidine uptake. EHNA at a concentration of 50 muM also potentiated the inhibitory effects on thymidine uptake of dibutyryl cyclic AMP, butyric acid, norepinephrine, and isoproterenol, but not theophylline. When mitogenesis was assayed by leucine incorporations, no synergy between EHNA and these compounds was apparent. Uridine relieved to some extent the inhibition of blastogenesis produced by adenosine and cyclic AMP, but not by dibutyryl cyclic AMP, norepinephreine, isoproterenol, or theophylline. Neither uridine alone nor uridine plus adenosine protected lymphocytes from the inhibitory effects of EHNA.

Authors

D A Carson, J E Seegmiller

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Total citations by year

Year: 2020 2019 2018 2015 2013 2012 2010 2009 2008 2006 2001 1998 1997 1995 1994 1992 1991 1990 1989 1988 1987 1986 1985 1984 1983 1982 1981 1980 1979 1978 1977 1976 Total
Citations: 1 1 1 1 1 1 1 2 3 1 1 3 1 7 2 1 2 3 2 2 3 6 5 8 8 8 7 11 13 17 13 4 140
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2008 (3)

Title and authors Publication Year
Novartis Foundation Symposia
EJ Campbell
Ciba Foundation Symposium 44 - Research and Medical Practice: Their Interaction 2008
Modulation of signal transduction pathways in lymphocytes due to sub-lethal toxicity of chlorinated phenol
A Limaye, RS Kashyap, A Kapley, S Galande, HJ Purohit, HF Daginawala, GM Taori
Toxicology Letters 2008
Adenosine deaminase activity in sera of patients with visceral leishmaniasis in India
K Tripathi, R Kumar, K Bharti, P Kumar, RK Shrivastav, S Sundar, K Pai
Clinica Chimica Acta 2008

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