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. 1990 Oct;71(2):196–201.

Selective modulation of the natural killer activity of murine intestinal intraepithelial leucocytes by the neuropeptide substance P.

K Croitoru 1, P B Ernst 1, J Bienenstock 1, I Padol 1, A M Stanisz 1
PMCID: PMC1384303  PMID: 1699880

Abstract

Neuropeptides can influence immune effector cell function at both systemic and mucosal immune sites. We examined the ability of substance P (SP) to modulate the natural killer (NK) activity of intestinal intraepithelial leucocytes (IEL). Yac-1 killing by IEL but not splenic cells was increased after either 18 hr preincubation or 6 hr of co-incubation with SP. We also examined the NK activity of IEL and spleen isolated from mice treated with SP in vivo. The selective increase in NK activity of IEL occurred without any demonstrable change in the number or phenotype of the IEL. The IEL responsive to SP in vivo and induced in vivo by SP were both Thy-1- and did not kill the NK insensitive mastocytoma cell line P815. Lastly, we examined the ability of SP to induce the release of interleukin-2 (IL-2) and IL-4 from IEL after 6 and 18 hr of in vitro culture. No increase in the release of these cytokines was observed, suggesting that IL-2 and IL4 are not involved in the local augmentation of IEL NK activity by SP. These observations suggest that SP has a selective stimulatory effect on intestinal activity and may play a role in the regulation of intestinal cell-mediated immunity.

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Selected References

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  1. Ader R., Cohen N. Behaviorally conditioned immunosuppression. Psychosom Med. 1975 Jul-Aug;37(4):333–340. doi: 10.1097/00006842-197507000-00007. [DOI] [PubMed] [Google Scholar]
  2. Carman P. S., Ernst P. B., Rosenthal K. L., Clark D. A., Befus A. D., Bienenstock J. Intraepithelial leukocytes contain a unique subpopulation of NK-like cytotoxic cells active in the defense of gut epithelium to enteric murine coronavirus. J Immunol. 1986 Mar 1;136(5):1548–1553. [PubMed] [Google Scholar]
  3. Danek A., O'Dorisio M. S., O'Dorisio T. M., George J. M. Specific binding sites for vasoactive intestinal polypeptide on nonadherent peripheral blood lymphocytes. J Immunol. 1983 Sep;131(3):1173–1177. [PubMed] [Google Scholar]
  4. Djeu J. Y., Heinbaugh J. A., Holden H. T., Herberman R. B. Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol. 1979 Jan;122(1):175–181. [PubMed] [Google Scholar]
  5. Ernst P. B., Petit A., Befus A. D., Clark D. A., Rosenthal K. L., Ishizaka T., Bienenstock J. Murine intestinal intraepithelial lymphocytes II. Comparison of freshly isolated and cultured intraepithelial lymphocytes. Eur J Immunol. 1985 Mar;15(3):216–221. doi: 10.1002/eji.1830150303. [DOI] [PubMed] [Google Scholar]
  6. Flexman J. P., Shellam G. R., Mayrhofer G. Natural cytotoxicity, responsiveness to interferon and morphology of intra-epithelial lymphocytes from the small intestine of the rat. Immunology. 1983 Apr;48(4):733–741. [PMC free article] [PubMed] [Google Scholar]
  7. Good M. F., Powell L. W., Halliday J. W. IL-2 and IL-4 can co-modulate the generation of cytotoxic T cells through CD8- CD4- splenic lymphocytes. Immunology. 1989 Jun;67(2):225–230. [PMC free article] [PubMed] [Google Scholar]
  8. Hartung H. P., Wolters K., Toyka K. V. Substance P: binding properties and studies on cellular responses in guinea pig macrophages. J Immunol. 1986 May 15;136(10):3856–3863. [PubMed] [Google Scholar]
  9. Henney C. S., Kuribayashi K., Kern D. E., Gillis S. Interleukin-2 augments natural killer cell activity. Nature. 1981 May 28;291(5813):335–338. doi: 10.1038/291335a0. [DOI] [PubMed] [Google Scholar]
  10. Hewlett G., Stünkel K. G., Schlumberger H. D. A method for the quantitation of interleukin-2 activity. J Immunol Methods. 1989 Feb 24;117(2):243–246. doi: 10.1016/0022-1759(89)90146-4. [DOI] [PubMed] [Google Scholar]
  11. Klein J. R., Kagnoff M. F. Nonspecific recruitment of cytotoxic effector cells in the intestinal mucosa of antigen-primed mice. J Exp Med. 1984 Dec 1;160(6):1931–1936. doi: 10.1084/jem.160.6.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koch T. R., Carney J. A., Go V. L. Distribution and quantitation of gut neuropeptides in normal intestine and inflammatory bowel diseases. Dig Dis Sci. 1987 Apr;32(4):369–376. doi: 10.1007/BF01296290. [DOI] [PubMed] [Google Scholar]
  13. Lotz M., Vaughan J. H., Carson D. A. Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science. 1988 Sep 2;241(4870):1218–1221. doi: 10.1126/science.2457950. [DOI] [PubMed] [Google Scholar]
  14. Mathews P. M., Froelich C. J., Sibbitt W. L., Jr, Bankhurst A. D. Enhancement of natural cytotoxicity by beta-endorphin. J Immunol. 1983 Apr;130(4):1658–1662. [PubMed] [Google Scholar]
  15. Okada M., Kitahara M., Kishimoto S., Matsuda T., Hirano T., Kishimoto T. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol. 1988 Sep 1;141(5):1543–1549. [PubMed] [Google Scholar]
  16. Ottaway C. A., Bernaerts C., Chan B., Greenberg G. R. Specific binding of vasoactive intestinal peptide to human circulating mononuclear cells. Can J Physiol Pharmacol. 1983 Jul;61(7):664–671. doi: 10.1139/y83-103. [DOI] [PubMed] [Google Scholar]
  17. Ottaway C. A., Greenberg G. R. Interaction of vasoactive intestinal peptide with mouse lymphocytes: specific binding and the modulation of mitogen responses. J Immunol. 1984 Jan;132(1):417–423. [PubMed] [Google Scholar]
  18. Ottaway C. A. In vitro alteration of receptors for vasoactive intestinal peptide changes the in vivo localization of mouse T cells. J Exp Med. 1984 Oct 1;160(4):1054–1069. doi: 10.1084/jem.160.4.1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Payan D. G., Brewster D. R., Goetzl E. J. Specific stimulation of human T lymphocytes by substance P. J Immunol. 1983 Oct;131(4):1613–1615. [PubMed] [Google Scholar]
  20. Payan D. G., Brewster D. R., Goetzl E. J. Stereospecific receptors for substance P on cultured human IM-9 lymphoblasts. J Immunol. 1984 Dec;133(6):3260–3265. [PubMed] [Google Scholar]
  21. Petit A., Ernst P. B., Befus A. D., Clark D. A., Rosenthal K. L., Ishizaka T., Bienenstock J. Murine intestinal intraepithelial lymphocytes I. Relationship of a novel Thy-1-,Lyt-1-,Lyt-2+, granulated subpopulation to natural killer cells and mast cells. Eur J Immunol. 1985 Mar;15(3):211–215. doi: 10.1002/eji.1830150302. [DOI] [PubMed] [Google Scholar]
  22. Powers G. D., Abbas A. K., Miller R. A. Frequencies of IL-2- and IL-4-secreting T cells in naive and antigen-stimulated lymphocyte populations. J Immunol. 1988 May 15;140(10):3352–3357. [PubMed] [Google Scholar]
  23. Rola-Pleszczynski M., Bolduc D., St-Pierre S. The effects of vasoactive intestinal peptide on human natural killer cell function. J Immunol. 1985 Oct;135(4):2569–2573. [PubMed] [Google Scholar]
  24. Scicchitano R., Biennenstock J., Stanisz A. M. In vivo immunomodulation by the neuropeptide substance P. Immunology. 1988 Apr;63(4):733–735. [PMC free article] [PubMed] [Google Scholar]
  25. Scicchitano R., Dazin P., Bienenstock J., Payan D. G., Stanisz A. M. Distribution of somatostatin receptors on murine spleen and Peyer's patch T and B lymphocytes. Brain Behav Immun. 1987 Jun;1(2):173–184. doi: 10.1016/0889-1591(87)90019-5. [DOI] [PubMed] [Google Scholar]
  26. Shanahan F., Denburg J. A., Fox J., Bienenstock J., Befus D. Mast cell heterogeneity: effects of neuroenteric peptides on histamine release. J Immunol. 1985 Aug;135(2):1331–1337. [PubMed] [Google Scholar]
  27. Stanisz A. M., Befus D., Bienenstock J. Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen. J Immunol. 1986 Jan;136(1):152–156. [PubMed] [Google Scholar]
  28. Stanisz A. M., Scicchitano R., Dazin P., Bienenstock J., Payan D. G. Distribution of substance P receptors on murine spleen and Peyer's patch T and B cells. J Immunol. 1987 Aug 1;139(3):749–754. [PubMed] [Google Scholar]
  29. Stead R. H., Tomioka M., Quinonez G., Simon G. T., Felten S. Y., Bienenstock J. Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves. Proc Natl Acad Sci U S A. 1987 May;84(9):2975–2979. doi: 10.1073/pnas.84.9.2975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tagliabue A., Befus A. D., Clark D. A., Bienenstock J. Characteristics of natural killer cells in the murine intestinal epithelium and lamina propria. J Exp Med. 1982 Jun 1;155(6):1785–1796. doi: 10.1084/jem.155.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Targan S., Britvan L., Kendal R., Vimadalal S., Soll A. Isolation of spontaneous and interferon inducible natural killer like cells from human colonic mucosa: lysis of lymphoid and autologous epithelial target cells. Clin Exp Immunol. 1983 Oct;54(1):14–22. [PMC free article] [PubMed] [Google Scholar]
  32. Tosato G., Pike S. E. Interferon-beta 2/interleukin 6 is a co-stimulant for human T lymphocytes. J Immunol. 1988 Sep 1;141(5):1556–1562. [PubMed] [Google Scholar]
  33. Wagner F., Fink R., Hart R., Dancygier H. Substance P enhances interferon-gamma production by human peripheral blood mononuclear cells. Regul Pept. 1987 Dec;19(5-6):355–364. doi: 10.1016/0167-0115(87)90177-7. [DOI] [PubMed] [Google Scholar]

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