FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Clin Invest / In vitro of adenosine on lymphocytes and erythrocytes from h...
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.
Get Full Text
Publication Date: 1979-07-01 PubMed ID: 447864PubMed Central: PMC372094DOI: 10.1172/JCI109468Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

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

      References

      This article includes 51 references
      1. HALL JG. Adenosine deaminase activity in lymphoid cells during antibody production.. Aust J Exp Biol Med Sci 1963 Feb;41:93-7.
        pubmed: 13952110doi: 10.1038/icb.1963.8google scholar: lookup
      2. LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent.. J Biol Chem 1951 Nov;193(1):265-75.
        pubmed: 14907713
      3. Johnson SM, North ME, Asherson GL, Allsop J, Watts RW, Webster AD. Lymphocyte purine 5'-nucleotidase edficiency in primary hypogammaglobulinaemia.. Lancet 1977 Jan 22;1(8004):168-70.
        pubmed: 64699doi: 10.1016/s0140-6736(77)91765-2google scholar: lookup
      4. Perryman LE, Buening GM, McGuire TC, Torbeck RL, Poppie MJ, Sale GE. Fetal tissue transplantation for immunotherapy of combined immunodeficiency in horses.. Clin Immunol Immunopathol 1979 Feb;12(2):238-51.
        pubmed: 33778doi: 10.1016/0090-1229(79)90012-6google scholar: lookup
      5. Edwards NL, Magilavy DB, Cassidy JT, Fox IH. Lymphocyte ecto-5'-nucleotidase deficiency in agammaglobulinemia.. Science 1978 Aug 18;201(4356):628-30.
        pubmed: 27864doi: 10.1126/science.27864google scholar: lookup
      6. Schwartz AL, Stern RC, Polmar SH. Demonstration of adenosine receptor on human lymphocytes in vitro and its possible role in the adenosine deaminase-deficient form of severe combined immunodeficiency.. Clin Immunol Immunopathol 1978 Apr;9(4):499-505.
        pubmed: 206401doi: 10.1016/0090-1229(78)90146-0google scholar: lookup
      7. Perryman LE, McGuire TC, Crawford TB. Maintenance of foals with combined immunodeficiency: causes and control of secondary infections.. Am J Vet Res 1978 Jun;39(6):1043-7.
        pubmed: 208432
      8. Carson DA, Kaye J, Seegmiller JE. Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency: possible role of nucleoside kinase(s).. Proc Natl Acad Sci U S A 1977 Dec;74(12):5677-81.
        pubmed: 202960doi: 10.1073/pnas.74.12.5677google scholar: lookup
      9. Hershfield MS, Snyder FF, Seegmiller JE. Adenine and adenosine are toxic to human lymphoblast mutants defective in purine salvage enzymes.. Science 1977 Sep 23;197(4310):1284-7.
        pubmed: 197600doi: 10.1126/science.197600google scholar: lookup
      10. Schmalstieg FC, Nelson JA, Mills GC, Monahan TM, Goldman AS, Goldblum RM. Increased purine nucleotides in adenosine deaminase-deficient lymphocytes.. J Pediatr 1977 Jul;91(1):48-51.
        pubmed: 195028doi: 10.1016/s0022-3476(77)80442-3google scholar: lookup
      11. Perryman LE, McGuire TC. Mixed lymphocyte culture responses in combined immunodeficiency of horses.. Transplantation 1978 Feb;25(2):50-2.
        pubmed: 146281doi: 10.1097/00007890-197802000-00002google scholar: lookup
      12. Castles JJ, Gershwin ME, Saito W, Ardans A, Osburn B. The activity of purine salvage pathway enzymes in murine and horse models of congenital and acquired dysimmunity.. Dev Comp Immunol 1977 Apr;1(2):165-73.
        pubmed: 416973doi: 10.1016/s0145-305x(77)80009-8google scholar: lookup
      13. Cohen A, Gudas LJ, Ammann AJ, Staal GE, Martin DW Jr. Deoxyguanosine triphosphate as a possible toxic metabolite in the immunodeficiency associated with purine nucleoside phosphorylase deficiency.. J Clin Invest 1978 May;61(5):1405-9.
        pubmed: 96138doi: 10.1172/JCI109058google scholar: lookup
      14. Donofrio J, Coleman MS, Hutton JJ, Daoud A, Lampkin B, Dyminski J. Overproduction of adenine deoxynucleosides and deoxynucletides in adenosine deaminase deficiency with severe combined immunodeficiency disease.. J Clin Invest 1978 Oct;62(4):884-7.
        pubmed: 308954doi: 10.1172/JCI109201google scholar: lookup
      15. Poppie MJ, McGuire TC. Combined immunodeficiency in foals in Arabian breeding: evaluation of mode of inheritance and estimation of prevalence of affected foals and carrier mares and stallions.. J Am Vet Med Assoc 1977 Jan 1;170(1):31-3.
        pubmed: 299745
      16. Cohen A, Hirschhorn R, Horowitz SD, Rubinstein A, Polmar SH, Hong R, Martin DW Jr. Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency.. Proc Natl Acad Sci U S A 1978 Jan;75(1):472-6.
        pubmed: 272665doi: 10.1073/pnas.75.1.472google scholar: lookup
      17. Hodgin EC, McGuire TC, Perryman LE, Grant BD. Evaluation of delayed hypersensitivity responses in normal horses and immunodeficient foals.. Am J Vet Res 1978 Jul;39(7):1161-7.
        pubmed: 677535
      18. Buening GM, Perryman LE, McGuire TC. Immunoglobulins and secretory component in the external secretions of foals with combined immunodeficiency.. Infect Immun 1978 Feb;19(2):695-8.
        pubmed: 631895doi: 10.1128/iai.19.2.695-698.1978google scholar: lookup
      19. Coleman MS, Donofrio J, Hutton JJ, Hahn L, Daoud A, Lampkin B, Dyminski J. Identification and quantitation of adenine deoxynucleotides in erythrocytes of a patient with adenosine deaminase deficiency and severe combined immunodeficiency.. J Biol Chem 1978 Mar 10;253(5):1619-26.
        pubmed: 627559
      20. Hirschhorn R, Sela E. Adenosine deaminase and immunodeficiency: an in vitro model.. Cell Immunol 1977 Aug;32(2):350-60.
        pubmed: 902324doi: 10.1016/0008-8749(77)90211-8google scholar: lookup
      21. Perryman LE, McGuire TC, Hilbert BJ. Selective immunoglobulin M deficiency in foals.. J Am Vet Med Assoc 1977 Jan 15;170(2):212-5.
        pubmed: 833046
      22. Adams A, Harkness RA. Adenosine deaminase activity in thymus and other human tissues.. Clin Exp Immunol 1976 Dec;26(3):647-9.
        pubmed: 1009688
      23. Polmar SH, Stern RC, Schwartz AL, Wetzler EM, Chase PA, Hirschhorn R. Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency.. N Engl J Med 1976 Dec 9;295(24):1337-43.
        pubmed: 980079doi: 10.1056/NEJM197612092952402google scholar: lookup
      24. Jenkins T, Rabson AR, Nurse GT, Lane AB. Deficiency of adenosine deaminase not associated with severe combined immunodeficiency.. J Pediatr 1976 Nov;89(5):732-6.
        pubmed: 978319doi: 10.1016/s0022-3476(76)80792-5google scholar: lookup
      25. Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity.. Lancet 1972 Nov 18;2(7786):1067-9.
        pubmed: 4117384doi: 10.1016/s0140-6736(72)92345-8google scholar: lookup
      26. McGuire TC, Poppie MJ, Banks KL. Combined (B- and T-lymphocyte) immunodeficiency: a fatal genetic disease in Arabian foals.. J Am Vet Med Assoc 1974 Jan 1;164(1):70-6.
        pubmed: 4358832
      27. Kaukel E, Fuhrmann U, Hilz H. Divergent action of cAMP and dibutyryl cAMP on macromolecular synthesis in HeLa S3 cultures.. Biochem Biophys Res Commun 1972 Sep 26;48(6):1516-24.
        pubmed: 4342713doi: 10.1016/0006-291x(72)90886-8google scholar: lookup
      28. Hilz H, Kaukel E. Divergent action mechanism of cAMP and dibutyryl cAMP on cell proliferation and macromolecular synthesis in HeLa S3 cultures.. Mol Cell Biochem 1973 Jun 27;1(2):229-39.
        pubmed: 4356738doi: 10.1007/BF01659332google scholar: lookup
      29. Shen LC, Fall L, Walton GM, Atkinson DE. Interaction between energy charge and metabolite modulation in the regulation of enzymes of amphibolic sequences. Phosphofructokinase and pyruvate dehydrogenase.. Biochemistry 1968 Nov;7(11):4041-5.
        pubmed: 4301881doi: 10.1021/bi00851a035google scholar: lookup
      30. Smith JW, Steiner AL, Parker CW. Human lymphocytic metabolism. Effects of cyclic and noncyclic nucleotides on stimulation by phytohemagglutinin.. J Clin Invest 1971 Feb;50(2):442-8.
        pubmed: 4322078doi: 10.1172/JCI106511google scholar: lookup
      31. McGuire TC, Poppie MJ. Hypogammaglobulinemia and thymic hypoplasia in horses: a primary combined immunodeficiency disorder.. Infect Immun 1973 Aug;8(2):272-7.
        pubmed: 4199158doi: 10.1128/iai.8.2.272-277.1973google scholar: lookup
      32. Brown PR, Agarwal RP, Gell J, Parks RE Jr. Nucleotide metabolism in the whole blood of various vertebrates: enzyme levels and the use of high pressure liquid chromatography for the determination of nucleotide patterns.. Comp Biochem Physiol B 1972 Dec 15;43(4):891-904.
        pubmed: 4197029doi: 10.1016/0305-0491(72)90233-7google scholar: lookup
      33. Giblett ER, Ammann AJ, Wara DW, Sandman R, Diamond LK. Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity.. Lancet 1975 May 3;1(7914):1010-3.
        pubmed: 48676doi: 10.1016/s0140-6736(75)91950-9google scholar: lookup
      34. Wolberg G, Zimmerman TP, Hiemstra K, Winston M, Chu LC. Adenosine inhibition of lymphocyte-mediated cytolysis: possible role of cyclic adenosine monophosphate.. Science 1975 Mar 14;187(4180):957-9.
        pubmed: 167434doi: 10.1126/science.167434google scholar: lookup
      35. Carson DA, Seegmiller JE. Effect of adenosine deaminase inhibition upon human lymphocyte blastogenesis.. J Clin Invest 1976 Feb;57(2):274-82.
        pubmed: 176177doi: 10.1172/JCI108278google scholar: lookup
      36. Hovi T, Smyth JF, Allison AC, Williams SC. Role of adenosine deaminase in lymphocyte proliferation.. Clin Exp Immunol 1976 Mar;23(3):395-403.
        pubmed: 133008
      37. Green H, Chan T. Pyrimidine starvation induced by adenosine in fibroblasts and lymphoid cells: role of adenosine deaminase.. Science 1973 Nov 23;182(4114):836-7.
        pubmed: 4795749doi: 10.1126/science.182.4114.836google scholar: lookup
      38. McGuire TC, Pollara B, Moore JJ, Poppie MJ. Evaluation of adenosine deaminase and other purine salvage pathway enzymes in horses with combined immunodeficiency.. Infect Immun 1976 Mar;13(3):995-7.
        pubmed: 818021doi: 10.1128/iai.13.3.995-997.1976google scholar: lookup
      39. McGuire TC, Banks KL, Poppie MJ. Combined immunodeficiency in horses: characterization of the lymphocyte defect.. Clin Immunol Immunopathol 1975 Mar;3(4):555-66.
        pubmed: 803888doi: 10.1016/0090-1229(75)90080-xgoogle scholar: lookup
      40. Khym JX. An analytical system for rapid separation of tissue nucleotides at low pressures on conventional anion exchangers.. Clin Chem 1975 Aug;21(9):1245-52.
        pubmed: 1097132
      41. Swedes JS, Sedo RJ, Atkinson DE. Relation of growth and protein synthesis to the adenylate energy charge in an adenine-requiring mutant of Escherichia coli.. J Biol Chem 1975 Sep 10;250(17):6930-8.
        pubmed: 1099099
      42. Parks RE Jr, Crabtree GW, Kong CM, Agarwal RP, Agarwal KC, Scholar EM. Incorporation of analog purine nucleosides into the formed elements of human blood: erythrocytes, platelets, and lymphocytes.. Ann N Y Acad Sci 1975 Aug 8;255:412-34.
        pubmed: 1103687doi: 10.1111/j.1749-6632.1975.tb29249.xgoogle scholar: lookup
      43. Mills GC, Schmalstieg FC, Trimmer KB, Goldman AS, Goldblum RM. Purine metabolism in adenosine deaminase deficiency.. Proc Natl Acad Sci U S A 1976 Aug;73(8):2867-71.
        pubmed: 1066699doi: 10.1073/pnas.73.8.2867google scholar: lookup
      44. Snyder FF, Mendelsohn J, Seegmiller JE. Adenosine metabolism in phytohemagglutinin-stimulated human lymphocytes.. J Clin Invest 1976 Sep;58(3):654-66.
        pubmed: 956393doi: 10.1172/JCI108512google scholar: lookup
      45. Agarwal RP, Crabtree GW, Parks RE Jr, Nelson JA, Keightley R, Parkman R, Rosen FS, Stern RC, Polmar SH. Purine nucleoside metabolism in the erythrocytes of patients with adenosine deaminase deficiency and severe combined immunodeficiency.. J Clin Invest 1976 Apr;57(4):1025-35.
        pubmed: 947948doi: 10.1172/JCI108344google scholar: lookup
      46. Ballet JJ, Insel R, Merler E, Rosen FS. Inhibition of maturation of human precursor lymphocytes by coformycin, an inhibitor of the enzyme adenosine deaminase.. J Exp Med 1976 May 1;143(5):1271-6.
        pubmed: 1262787doi: 10.1084/jem.143.5.1271google scholar: lookup
      47. Fox IH, Keystone EC, Gladman DD, Moore M, Cane D. Inhibition of mitogen mediated lymphocyte blastogenesis by adenosine.. Immunol Commun 1975;4(5):419-27.
        pubmed: 1205504doi: 10.3109/08820137509057330google scholar: lookup
      48. McGuire TC, Banks KL, Poppie MJ. Animal model of human disease. Combined immunodeficiency (severe), Swiss-type agammaglobulinemia.. Am J Pathol 1975 Sep;80(3):551-4.
        pubmed: 1163643
      49. Banks KL, McGuire TC. Surface receptors on neutrophils and monocytes from immunodeficient and normal horses.. Immunology 1975 Mar;28(3):581-8.
        pubmed: 1126740
      50. Eilermann LJ, Slater EC. The phosphate potential generated by membrane fragments of Azotobacter vinelandii.. Biochim Biophys Acta 1970 Aug 4;216(1):226-8.
        pubmed: 5497188doi: 10.1016/0005-2728(70)90175-1google scholar: lookup
      51. Brown PR. The rapid separation of nucleotides in cell extracts using high-pressure liquid chromatography.. J Chromatogr 1970 Oct 21;52(2):257-72.
        pubmed: 5474279doi: 10.1016/s0021-9673(01)96573-2google scholar: lookup

      Citations

      This article has been cited 0 times.
      Subscribe to our newsletter
      Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.