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. 1983 Nov;54(2):493–500.

Modulation of human natural killer cell activity by pharmacological mediators.

T J Hall, S H Chen, J Brostoff, P M Lydyard
PMCID: PMC1535881  PMID: 6317242

Abstract

We have studied the effects of various pharmacological mediators on human NK cell activity. Prostaglandin E2 (PGE2) inhibits NK cell activity in a dose-dependent fashion, whereas PGF2 alpha has no significant effect over the same concentration range. Histamine at high doses (10(-4) M) induced a small but significant inhibition of NK cell activity which was mimicked by both H1 and H2 specific histamine receptor agonists. Inhibition of endogenous prostaglandin production by indomethacin did not alter NK cell activity. Inhibition of NK activity by cAMP but not cGMP analogues, together with other data presented suggests that the mechanism of PGE2-induced inhibition of NK cell activity is not due to impairment of effector cell movement or effector: target cell interaction, but through the adenylate cyclase system which modulates the killing process.

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Selected References

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  1. Bray M. A., Powell R. G., Lydyard P. M. Prostaglandin generation by separated human blood mononuclear cell fractions. Int J Immunopharmacol. 1981;3(4):377–381. doi: 10.1016/0192-0561(81)90033-3. [DOI] [PubMed] [Google Scholar]
  2. Brostoff J., Pack S., Lydyard P. M. Histamine suppression of lymphocyte activation. Clin Exp Immunol. 1980 Mar;39(3):739–745. [PMC free article] [PubMed] [Google Scholar]
  3. Cudkowicz G., Hochman P. S. Do natural killer cells engage in regulated reactions against self to ensure homeostasis? Immunol Rev. 1979;44:13–41. doi: 10.1111/j.1600-065x.1979.tb00266.x. [DOI] [PubMed] [Google Scholar]
  4. Dobloug J. H., Førre O., Kvien T. K., Egeland T., Degré M. Natural killer (NK) cell activity of peripheral blood, synovial fluid, and synovial tissue lymphocytes from patients with rheumatoid arthritis and juvenile rheumatoid arthritis. Ann Rheum Dis. 1982 Oct;41(5):490–494. doi: 10.1136/ard.41.5.490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Droller M. J., Schneider M. U., Perlmann P. A possible role of prostaglandins in the inhibition of natural and antibody-dependent cell-mediated cytotoxicity against tumor cells. Cell Immunol. 1978 Aug;39(1):165–177. doi: 10.1016/0008-8749(78)90091-6. [DOI] [PubMed] [Google Scholar]
  6. Goodwin J. S., DeHoratius R., Israel H., Peake G. T., Messner R. P. Suppressor cell function in sarcoidosis. Ann Intern Med. 1979 Feb;90(2):169–173. doi: 10.7326/0003-4819-90-2-169. [DOI] [PubMed] [Google Scholar]
  7. Goodwin J. S., Kaszubowski P. A., Williams R. C., Jr Cyclic adenosine monophosphate response to prostaglandin E2 on subpopulations of human lymphocytes. J Exp Med. 1979 Nov 1;150(5):1260–1264. doi: 10.1084/jem.150.5.1260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goodwin J. S., Messner R. P., Bankhurst A. D., Peake G. T., Saiki J. H., Williams R. C., Jr Prostaglandin-producing suppressor cells in Hodgkin's disease. N Engl J Med. 1977 Nov 3;297(18):963–968. doi: 10.1056/NEJM197711032971802. [DOI] [PubMed] [Google Scholar]
  9. Grimm E., Bonavida B. Mechanism of cell-mediated cytotoxicity at the single cell level. I. Estimation of cytotoxic T lymphocyte frequency and relative lytic efficiency. J Immunol. 1979 Dec;123(6):2861–2869. [PubMed] [Google Scholar]
  10. Gupta S., Fernandes G. Spontaneous and antibody-dependent cellular cytotoxicity by lymphocyte subpopulations in peripheral blood and spleen from adult untreated patients with Hodgkin's disease. Clin Exp Immunol. 1981 Jul;45(1):205–214. [PMC free article] [PubMed] [Google Scholar]
  11. Hansson M., Kärre K., Kiessling R., Roder J., Andersson B., Häyry P. Natural NK-cell targets in the mouse thymus: characteristics of the sensitive cell population. J Immunol. 1979 Aug;123(2):765–771. [PubMed] [Google Scholar]
  12. Jondal M., Pross H. Surface markers on human b and t lymphocytes. VI. Cytotoxicity against cell lines as a functional marker for lymphocyte subpopulations. Int J Cancer. 1975 Apr 15;15(4):596–605. doi: 10.1002/ijc.2910150409. [DOI] [PubMed] [Google Scholar]
  13. Jondal M., Spine C., Targan S. Human spontaneous killer cells selective for tumour-derived target cells. Nature. 1978 Mar 2;272(5648):62–64. doi: 10.1038/272062a0. [DOI] [PubMed] [Google Scholar]
  14. Kaliner M. Human lung tissue and anaphylaxis. I. The role of cyclic GMP as a modulator of the immunologically induced secretory process. J Allergy Clin Immunol. 1977 Sep;60(3):204–211. doi: 10.1016/0091-6749(77)90125-7. [DOI] [PubMed] [Google Scholar]
  15. Katz P., Zaytoun A. M., Fauci A. S. Mechanisms of human cell-mediated cytotoxicity. I. Modulation of natural killer cell activity by cyclic nucleotides. J Immunol. 1982 Jul;129(1):287–296. [PubMed] [Google Scholar]
  16. Melmon K. L., Rocklin R. E., Rosenkranz R. P. Autacoids as modulators of the inflammatory and immune response. Am J Med. 1981 Jul;71(1):100–106. doi: 10.1016/0002-9343(81)90264-3. [DOI] [PubMed] [Google Scholar]
  17. Mozes E., Weinstein Y., Bourne H. R., Melmon K. L., Shearer G. M. In vitro correction of antigen-induced immune suppression: effects of histamine, dibutyryl cyclic AMP and cholera enterotoxin. Cell Immunol. 1974 Mar 30;11(1-3):57–63. doi: 10.1016/0008-8749(74)90006-9. [DOI] [PubMed] [Google Scholar]
  18. Ortaldo J. R., Sharrow S. O., Timonen T., Herberman R. B. Determination of surface antigens on highly purified human NK cells by flow cytometry with monoclonal antibodies. J Immunol. 1981 Dec;127(6):2401–2409. [PubMed] [Google Scholar]
  19. Santoli D., Koprowski H. Mechanisms of activation of human natural killer cells against tumor and virus-infected cells. Immunol Rev. 1979;44:125–163. doi: 10.1111/j.1600-065x.1979.tb00269.x. [DOI] [PubMed] [Google Scholar]
  20. Timonen T., Ortaldo J. R., Herberman R. B. Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med. 1981 Mar 1;153(3):569–582. doi: 10.1084/jem.153.3.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. West W. H., Payne S. M., Weese J. L., Herberman R. B. Human T lymphocyte subpopulations: correlation between E-rosette-forming affinity and expression of the Fc receptor. J Immunol. 1977 Aug;119(2):548–554. [PubMed] [Google Scholar]

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