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Effects of Adenosine on Human Neutrophil Function and Cyclic AMP Content

  • Conference paper
Topics and Perspectives in Adenosine Research

Summary

The inhibitory effects of adenosine (Ado) on human neutrophil function have been investigated. N-Formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) induced neutrophil polarization (a characteristic change in neutrophil shape in response to a chemotactic stimulus), H2O2 production, and myeloperoxidase release were found to be suppressed by endogenously produced Ado. This partial inhibition of cell function was abrogated by addition of adenosine deaminase (ADA). All experiments were therefore conducted in the presence of ADA. FMLP-induced polarization, H2O2 production, and myeloperoxidase release of human neutrophils were inhibited by exogenously added Ado (in combination with 2′-deoxycoformycin to inactivate the ADA) and Ado analogues in the rank order of potency: 5′-N-ethylcarboxamide adenosine > 2-chloroadenosine ≅ Ado ≅ N6-(L-2-phenyl-isopropyl)adenosine > N6-(Z)-2-phenyl-isopropyl)adenosine. The inhibition of H2O2 production by the Ado analogues was potentiated by the nonmethylxanthine cyclic AMP phosphodiesterase inhibitor 4-(3-butoxy-4-methoxyben-zyl)-2-imidazolidinone (Ro 20-1724), whereas theophylline antagonized the inhibition. Exogenously added Ado (in combination with 2′-deoxycoformycin), like the four Ado analogues, induced elevations in neutrophil cyclic AMP levels, which were markedly potentiated by Ro 20-1724 and which occurred at nucleoside concentrations similar to those that were inhibitory to neutrophil function. These data provide evidence that three different elicited responses of human neutrophils may be modulated in vivo by physiological levels of Ado acting through adenylate cyclase-coupled Ado A2 receptors.

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Abbreviations

Ado:

adenosine

HBSS:

Hanks’ balanced salt solution containing 10 mMHEPES

ADA:

adenosine deaminase

BSA:

bovine serum albumin

FMLP:

N-formyl-L-methionyl-L-leucyl-L-phenylalanine

3H]FMLP:

formyl-L-methionyl-L-leucyl-L-phenylala-nine, N-[phenylalanine-ring-2,6-3H(N)]

DMSO:

dimethyl sulfoxide

dCF:

2′-deoxycoformycin

Ro 20-1724:

4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone

NECA:

5′-N-ethylcarboxamide adenosine

Cl-Ado:

2-chloroadenosine

L-PIA:

N6-(L-2-phenyl-isopropyl)adenosine or (-)-N6-(R-phenyl-isopropyl)adenosine

D-PIA:

N6-(D-2-phenyl-isopropyl)adenosine or (+)-N6-(S-phe-nyl-isopropyl)adenosine

HVA:

homovanillic acid

HRP:

horseradish peroxidase

GBSS:

Gey’s balanced salt solution containing 2% bovalbumin

HPLC:

high-performance liquid chromato-graphy

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Authors and Affiliations

  1. Wellcome Research Laboratories, Research Triangle Park, NC, 27709, USA

    M. A. Iannone, T. P. Zimmerman, R. Reynolds-Vaughn & G. Wolberg

Authors
  1. M. A. Iannone
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  2. T. P. Zimmerman
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  3. R. Reynolds-Vaughn
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  4. G. Wolberg
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Editor information

Editors and Affiliations

  1. Physiologisches Institut, Universität München, Pettenkoferstraße 12, 8000, München 2, Federal Republic of Germany

    Eckehart Gerlach  & Bernhard Friedrich Becker  & 

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© 1987 Springer-Verlag Berlin Heidelberg

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Iannone, M.A., Zimmerman, T.P., Reynolds-Vaughn, R., Wolberg, G. (1987). Effects of Adenosine on Human Neutrophil Function and Cyclic AMP Content. In: Gerlach, E., Becker, B.F. (eds) Topics and Perspectives in Adenosine Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45619-0_23

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  • DOI: https://doi.org/10.1007/978-3-642-45619-0_23

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-45621-3

  • Online ISBN: 978-3-642-45619-0

  • eBook Packages: Springer Book Archive

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