Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1991 Sep;85(3):493–497. doi: 10.1111/j.1365-2249.1991.tb05755.x

Beta-casomorphin (BCM) and human colonic lamina propria lymphocyte proliferation.

Y Elitsur 1, G D Luk 1
PMCID: PMC1535619  PMID: 1893631

Abstract

BCM is a milk-derived peptide with opiate-like properties which is absorbed through the gastrointestinal mucosa. It has been shown to affect gastrointestinal motility, absorption and secretion. Recently, modulation of the immune system by BCM was also reported. In this study we investigated the in vitro effect of BCM on the human mucosal immune response as represented by lamina propria lymphocyte (LPL) proliferation. Results show that BCM significantly inhibited concanavalin A (ConA) stimulated LPL DNA synthesis. BCM also inhibited ornithine decarboxylase activity (ODC) in ConA-stimulated LPL. Although BCM also inhibited 12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulated LPL DNA synthesis, the degree of inhibition was much lower than in ConA-stimulated LPL. The anti-proliferative effect of BCM was reversed by the opiate receptor antagonist, neloxone. Our results suggest that BCM may affect the human mucosal immune system, possibly via the opiate receptor.

Full text

PDF
493

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abb J., Bayliss G. J., Deinhardt F. Lymphocyte activation by the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA). J Immunol. 1979 May;122(5):1639–1642. [PubMed] [Google Scholar]
  2. Beaven M. A., Wilcox G., Terpstra G. K. A microprocedure for the measurement of 14CO2 release from [14C]carboxyl-labeled amino acids. Anal Biochem. 1978 Feb;84(2):638–641. doi: 10.1016/0003-2697(78)90089-1. [DOI] [PubMed] [Google Scholar]
  3. Bowlin T. L., McKown B. J., Sunkara P. S. The effect of alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on mitogen-induced interleukin 2 production. Immunopharmacology. 1987 Apr;13(2):143–147. doi: 10.1016/0162-3109(87)90051-8. [DOI] [PubMed] [Google Scholar]
  4. Brantl V., Pfeiffer A., Herz A., Henschen A., Lottspeich F. Antinociceptive potencies of beta-casomorphin analogs as compared to their affinities towards mu and delta opiate receptor sites in brain and periphery. Peptides. 1982 Sep-Oct;3(5):793–797. doi: 10.1016/0196-9781(82)90017-1. [DOI] [PubMed] [Google Scholar]
  5. Brown S. L., Van Epps D. E. Suppression of T lymphocyte chemotactic factor production by the opioid peptides beta-endorphin and met-enkephalin. J Immunol. 1985 May;134(5):3384–3390. [PubMed] [Google Scholar]
  6. Bull D. M., Bookman M. A. Isolation and functional characterization of human intestinal mucosal lymphoid cells. J Clin Invest. 1977 May;59(5):966–974. doi: 10.1172/JCI108719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elitsur Y., Bull A. W., Luk G. D. Modulation of human colonic lamina propria lymphocyte proliferation. Effect of bile acids and oxidized fatty acids. Dig Dis Sci. 1990 Feb;35(2):212–220. doi: 10.1007/BF01536765. [DOI] [PubMed] [Google Scholar]
  8. Elson C. O., Kagnoff M. F., Fiocchi C., Befus A. D., Targan S. Intestinal immunity and inflammation: recent progress. Gastroenterology. 1986 Sep;91(3):746–768. doi: 10.1016/0016-5085(86)90649-9. [DOI] [PubMed] [Google Scholar]
  9. Faith R. E., Liang H. J., Murgo A. J., Plotnikoff N. P. Neuroimmunomodulation with enkephalins: enhancement of human natural killer (NK) cell activity in vitro. Clin Immunol Immunopathol. 1984 Jun;31(3):412–418. doi: 10.1016/0090-1229(84)90093-x. [DOI] [PubMed] [Google Scholar]
  10. Gilman S. C., Schwartz J. M., Milner R. J., Bloom F. E., Feldman J. D. beta-Endorphin enhances lymphocyte proliferative responses. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4226–4230. doi: 10.1073/pnas.79.13.4226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hazum E., Chang K. J., Cuatrecasas P. Specific nonopiate receptors for beta-endorphin. Science. 1979 Sep 7;205(4410):1033–1035. doi: 10.1126/science.224457. [DOI] [PubMed] [Google Scholar]
  12. Hill D. J., Firer M. A., Shelton M. J., Hosking C. S. Manifestations of milk allergy in infancy: clinical and immunologic findings. J Pediatr. 1986 Aug;109(2):270–276. doi: 10.1016/s0022-3476(86)80384-5. [DOI] [PubMed] [Google Scholar]
  13. Koch G., Wiedemann K., Teschemacher H. Opioid activities of human beta-casomorphins. Naunyn Schmiedebergs Arch Pharmacol. 1985 Dec;331(4):351–354. doi: 10.1007/BF00500818. [DOI] [PubMed] [Google Scholar]
  14. Koski G., Klee W. A. Opiates inhibit adenylate cyclase by stimulating GTP hydrolysis. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4185–4189. doi: 10.1073/pnas.78.7.4185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leadem C. A., Kalra S. P. Effects of endogenous opioid peptides and opiates on luteinizing hormone and prolactin secretion in ovariectomized rats. Neuroendocrinology. 1985 Oct;41(4):342–352. doi: 10.1159/000124199. [DOI] [PubMed] [Google Scholar]
  16. Lopker A., Abood L. G., Hoss W., Lionetti F. J. Stereoselective muscarinic acetylcholine and opiate receptiors in human phagocytic leukocytes. Biochem Pharmacol. 1980 May 15;29(10):1361–1365. doi: 10.1016/0006-2952(80)90431-1. [DOI] [PubMed] [Google Scholar]
  17. Lord J. A., Waterfield A. A., Hughes J., Kosterlitz H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977 Jun 9;267(5611):495–499. doi: 10.1038/267495a0. [DOI] [PubMed] [Google Scholar]
  18. Mandler R. N., Biddison W. E., Mandler R., Serrate S. A. beta-Endorphin augments the cytolytic activity and interferon production of natural killer cells. J Immunol. 1986 Feb 1;136(3):934–939. [PubMed] [Google Scholar]
  19. Matthies H., Stark H., Hartrodt B., Ruethrich H. L., Spieler H. T., Barth A., Neubert K. Derivatives of beta-casomorphins with high analgesic potency. Peptides. 1984 May-Jun;5(3):463–470. doi: 10.1016/0196-9781(84)90070-6. [DOI] [PubMed] [Google Scholar]
  20. Mehrishi J. N., Mills I. H. Opiate receptors on lymphocytes and platelets in man. Clin Immunol Immunopathol. 1983 May;27(2):240–249. doi: 10.1016/0090-1229(83)90074-0. [DOI] [PubMed] [Google Scholar]
  21. Mustelin T., Pösö H., Andersson L. C. Role of G-proteins in T cell activation: non-hydrolysable GTP analogues induce early ornithine decarboxylase activity in human T lymphocytes. EMBO J. 1986 Dec 1;5(12):3287–3290. doi: 10.1002/j.1460-2075.1986.tb04641.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Parker F., Migliore-Samour D., Floc'h F., Zerial A., Werner G. H., Jollès J., Casaretto M., Zahn H., Jollès P. Immunostimulating hexapeptide from human casein: amino acid sequence, synthesis and biological properties. Eur J Biochem. 1984 Dec 17;145(3):677–682. doi: 10.1111/j.1432-1033.1984.tb08609.x. [DOI] [PubMed] [Google Scholar]
  23. Roder J. C., Klein M. Target-effector interaction in the natural killer cell system. IV. Modulation by cyclic nucleotides. J Immunol. 1979 Dec;123(6):2785–2790. [PubMed] [Google Scholar]
  24. Svedberg J., de Haas J., Leimenstoll G., Paul F., Teschemacher H. Demonstration of beta-casomorphin immunoreactive materials in in vitro digests of bovine milk and in small intestine contents after bovine milk ingestion in adult humans. Peptides. 1985 Sep-Oct;6(5):825–830. doi: 10.1016/0196-9781(85)90308-0. [DOI] [PubMed] [Google Scholar]
  25. Umbach M., Teschemacher H., Praetorius K., Hirschhäuser R., Bostedt H. Demonstration of a beta-casomorphin immunoreactive material in the plasma of newborn calves after milk intake. Regul Pept. 1985 Nov 7;12(3):223–230. doi: 10.1016/0167-0115(85)90063-1. [DOI] [PubMed] [Google Scholar]
  26. Van Epps D. E., Saland L., Taylor C., Williams R. C., Jr In vitro and in vivo effects of beta-endorphin and met-enkephalin on leukocyte locomotion. Prog Brain Res. 1983;59:361–374. doi: 10.1016/s0079-6123(08)63882-0. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES