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The Journal of clinical investigation1979; 64(1); 89-101; doi: 10.1172/JCI109468

In vitro of adenosine on lymphocytes and erythrocytes from horses with combined immunodeficiency.

Abstract: The effect of adenosine on the mitogenic response of peripheral blood lymphocytes (PBL) and on the nucleotide pools of erythrocytes from normal horses, horses heterozygous for the combined immunodeficiency (CID) trait (carriers), and foals with CID was studied. When PBL from normal, carrier, and CID horses were stimulated by phytohemagglutinin (PHA), concanavalin A, or pokeweed mitogen, [3H]thymidine uptake was inhibited by adenosine (0.1 microM) to 1.0 mM) in a dose-dependent manner. Adenosine (100 microM) mediated inhibition of [3H]thymidine uptake was prevented in both normal and carrier horse PBL by incubation with uridine. Uridine had no sparing effect on PBL from horses with CID. Differences were detected between human and horse PBL in response to adenosine and erythro-9(2-hydroxy-3-nonyl) adenine (EHNA), a competitive inhibitor of adenosine deaminase. In the first assay, mitogen-stimulated PBL from horses were more sensitive to adenosine. In the second assay, adenosine was added to PBL cultures at various times after PHA addition. Adenosine inhibited mitogenesis in horse PBL if added within the first 24 h. In human PBL cultures, adenosine inhibited mitogenesis only if added within the first 4 h. The third assay measured capacity of PHA-stimulated human and horse lymphocytes to escape inhibition by adenosine or EHNA. At the end of a 72-h culture period, horse PBL were still inhibited of mitogenesis in both human and horse PBL. With prolonged incubation (72 h), synergistic inhibition was detected only in horse PB. With high-pressure liquid chromatography, nucleotide levels in erythrocytes of normal, carrier, and CID horses were found to be similar. Incubation with adenosine produced a 1.5- to 2-fold increase in total adenine nucleotide pools in erythrocytes from all horses. However, these increases were accompanied by alterations in the relative amounts of the nucleotide components. This was seen as a significant decrease in the ATP:(AMP plus ADP plus ATP) ratio and energy charge in erythrocytes from normal horses. In contrast, the ATP:(AMP plus ADP plus ATP) ratio decreased only slightly in erythrocytes from CID horses, whereas no change in the energy charge was detected. The data from these studies indicate a difference in adenosine metabolism exists between human and horse lymphoyctes, and an abnormality may exist in purine metabolism or in an interconnecting pathway in horses with CID.
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Publication Date: 1979-07-01 PubMed ID: 447864PubMed Central: PMC372094DOI: 10.1172/JCI109468Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates how adenosine impacts the response of blood cells (lymphocytes and erythrocytes) in healthy horses, horses with genetic propensity for combined immunodeficiency (CID), and young horses with CID.

Research Focus and Methods

  • The study primarily focused on the effects of the molecule adenosine, on the response of peripheral blood lymphocytes (PBL) and erythrocytes in three categories of horses – healthy, carrier (with the genetic trait for CID) and those with active CID.
  • Adenosine showed dose-dependent inhibitory effects on lymphocyte activity in all three horse categories when these PBLs were stimulated with various mitogens (agents triggering cell division).
  • The inhibitory effect of adenosine was counteracted by incubation with uridine in healthy and carrier horses PBL, but not on horses with active CID.

Comparison Between Horse and Human Response

  • Contrasting responses to adenosine and a competitive inhibitor of adenosine deaminase, EHNA, were noted between human and horse PBLs. Research showed that horse PBLs were more sensitive to adenosine than human ones.
  • Moreover, adenosine inhibited cell division in horse PBL if added within the first 24 hours, while in human PBL, it was effective only if added within the first 4 hours.

Impact on Erythrocytes

  • Findings showed the adenosine incubation led to a 1.5- to 2-fold increase in total adenine nucleotide pool in erythrocytes in all categories of horses, but the increase was accompanied by changes in the relative amounts of the nucleotide components.
  • Specially, in erythrocytes from healthy horses there was significant decrease seen in the ATP:(AMP plus ADP plus ATP) ratio and energy charge. For CID horses though, the ATP ratio decreased slightly with no change in energy charge detected.

Conclusion

  • The study indicates that there are differences in the way human and horse lymphocytes process adenosine, hinting at an abnormality in the purine metabolism pathway or an interconnected pathway in horses with CID.

Cite This Article

APA
Magnuson NS, Perryman LE. (1979). In vitro of adenosine on lymphocytes and erythrocytes from horses with combined immunodeficiency. J Clin Invest, 64(1), 89-101. https://doi.org/10.1172/JCI109468

Publication

The Journal of clinical investigation
ISSN: 0021-9738
NlmUniqueID: 7802877
Country: United States
Language: English
Volume: 64
Issue: 1
Pages: 89-101

Researcher Affiliations

Magnuson, N S
    Perryman, L E

      MeSH Terms

      • Adenine / analogs & derivatives
      • Adenine / pharmacology
      • Adenine Nucleotides / blood
      • Adenosine / pharmacology
      • Adenosine Deaminase Inhibitors
      • Animals
      • Erythrocytes / cytology
      • Erythrocytes / drug effects
      • Erythrocytes / metabolism
      • Female
      • Horse Diseases / blood
      • Horses
      • Immunologic Deficiency Syndromes / blood
      • Immunologic Deficiency Syndromes / veterinary
      • Lymphocytes / cytology
      • Lymphocytes / drug effects
      • Lymphocytes / metabolism
      • Male
      • Mitogens / pharmacology
      • Nucleotides / blood
      • Thymidine / blood
      • Time Factors
      • Uridine / pharmacology

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