Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Aug;86(2):531–537. doi: 10.1172/JCI114740

Proenkephalin system in human polymorphonuclear cells. Production and release of a novel 1.0-kD peptide derived from synenkephalin.

O Vindrola 1, M R Padrós 1, A Sterin-Prync 1, A Ase 1, S Finkielman 1, V Nahmod 1
PMCID: PMC296756  PMID: 2117023

Abstract

In the hematopoietic system a pluripotent stem cell generates precursors for lymphoid and myeloid lineages. Proenkephalin-derived peptides were previously detected in differentiated lymphoid cells. We have studied whether the proenkephalin system is expressed in a typical differentiated cell of the myeloid lineage, the neutrophil. Human peripheral polymorphonuclear cells contain and release proenkephalin-derived peptides. The opioid portion of proenkephalin (met-enkephalin-containing peptides) was incompletely processed, resulting in the absence of low molecular weight products. The nonopioid synenkephalin (proenkephalin 1-70) molecule was completely processed to a 1.0-kD peptide derived from the COOH-terminal. This molecule was characterized in neutrophils by biochemical and immunocytochemical methods. The chemotactic peptide FMLP and the calcium ionophore A23187 induced the release of the proenkephalin-derived peptides, and this effect was potentiated by cytochalasin B. The materials secreted were similar to those present in the cell, although in the supernatant a higher proportion corresponded to more processed products. The 1.0-kD peptide was detected in human, bovine, and rat neutrophils, but the chromatographic pattern of synenkephalin-derived peptides suggests a differential posttranslational processing among species. These findings demonstrate the existence of the proenkephalin system in human neutrophils and the production and release of a novel 1.0-kD peptide derived from the synenkephalin molecule. The presence of opioid peptides in neutrophils suggests their participation in the inflammatory process, including a local analgesic effect.

Full text

PDF
532

Images in this article

534Image
on p.534
534Image
on p.534

Selected References

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

  1. Ase A., Vindrola O., Aloyz R., Inés M., Vida R., Finkielman S., Nahmod V. Association of endogenous synenkephalin containing peptides with intracellular membranes of bovine adrenal medulla. Biochem Biophys Res Commun. 1989 Feb 15;158(3):790–796. doi: 10.1016/0006-291x(89)92791-5. [DOI] [PubMed] [Google Scholar]
  2. Bainton D. F., Farquhar M. G. Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. II. Cytochemistry and electron microscopy of bone marrow cells. J Cell Biol. 1968 Nov;39(2):299–317. doi: 10.1083/jcb.39.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burgess T. L., Kelly R. B. Constitutive and regulated secretion of proteins. Annu Rev Cell Biol. 1987;3:243–293. doi: 10.1146/annurev.cb.03.110187.001331. [DOI] [PubMed] [Google Scholar]
  4. Bøyum A. Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol. 1976 Jun;Suppl 5:9–15. [PubMed] [Google Scholar]
  5. De Duve C., Wattiaux R. Functions of lysosomes. Annu Rev Physiol. 1966;28:435–492. doi: 10.1146/annurev.ph.28.030166.002251. [DOI] [PubMed] [Google Scholar]
  6. Dewald B., Bretz U., Baggiolini M. Release of gelatinase from a novel secretory compartment of human neutrophils. J Clin Invest. 1982 Sep;70(3):518–525. doi: 10.1172/JCI110643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Douglass J., Civelli O., Herbert E. Polyprotein gene expression: generation of diversity of neuroendocrine peptides. Annu Rev Biochem. 1984;53:665–715. doi: 10.1146/annurev.bi.53.070184.003313. [DOI] [PubMed] [Google Scholar]
  8. Fischer E. G., Falke N. E. Interaction of met-enkephalin with human granulocytes. Ann N Y Acad Sci. 1987;496:146–150. doi: 10.1111/j.1749-6632.1987.tb35757.x. [DOI] [PubMed] [Google Scholar]
  9. Folkesson R., Monstein H. J., Geijer T., Påhlman S., Nilsson K., Terenius L. Expression of the proenkephalin gene in human neuroblastoma cell lines. Brain Res. 1988 Apr;427(2):147–154. doi: 10.1016/0169-328x(88)90060-5. [DOI] [PubMed] [Google Scholar]
  10. Gennaro R., Dewald B., Horisberger U., Gubler H. U., Baggiolini M. A novel type of cytoplasmic granule in bovine neutrophils. J Cell Biol. 1983 Jun;96(6):1651–1661. doi: 10.1083/jcb.96.6.1651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Howells R. D., Kilpatrick D. L., Bailey L. C., Noe M., Udenfriend S. Proenkephalin mRNA in rat heart. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1960–1963. doi: 10.1073/pnas.83.6.1960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Höllt V. Opioid peptide processing and receptor selectivity. Annu Rev Pharmacol Toxicol. 1986;26:59–77. doi: 10.1146/annurev.pa.26.040186.000423. [DOI] [PubMed] [Google Scholar]
  13. Jesaitis A. J., Tolley J. O., Allen R. A. Receptor-cytoskeleton interactions and membrane traffic may regulate chemoattractant-induced superoxide production in human granulocytes. J Biol Chem. 1986 Oct 15;261(29):13662–13669. [PubMed] [Google Scholar]
  14. Joris J. L., Dubner R., Hargreaves K. M. Opioid analgesia at peripheral sites: a target for opioids released during stress and inflammation? Anesth Analg. 1987 Dec;66(12):1277–1281. [PubMed] [Google Scholar]
  15. Kaplan H. B., Edelson H. S., Friedman R., Weissmann G. The roles of degranulation and superoxide anion generation in neutrophil aggregation. Biochim Biophys Acta. 1982 Sep 13;721(1):55–63. doi: 10.1016/0167-4889(82)90023-4. [DOI] [PubMed] [Google Scholar]
  16. Kilpatrick D. L., Howells R. D., Noe M., Bailey L. C., Udenfriend S. Expression of preproenkephalin-like mRNA and its peptide products in mammalian testis and ovary. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7467–7469. doi: 10.1073/pnas.82.21.7467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klebanoff S. J., Hamon C. B. Role of myeloperoxidase-mediated antimicrobial systems in intact leukocytes. J Reticuloendothel Soc. 1972 Aug;12(2):170–196. [PubMed] [Google Scholar]
  18. Liston D. R., Vanderhaeghen J. J., Rossier J. Presence in brain of synenkephalin, a proenkephalin-immunoreactive protein which does not contain enkephalin. Nature. 1983 Mar 3;302(5903):62–65. doi: 10.1038/302062a0. [DOI] [PubMed] [Google Scholar]
  19. Liston D., Rossier J. Synenkephalin is coreleased with Met-enkephalin from neuronal terminals in vitro. Neurosci Lett. 1984 Jul 27;48(2):211–216. doi: 10.1016/0304-3940(84)90021-1. [DOI] [PubMed] [Google Scholar]
  20. Metters K. M., Rossier J. Affinity purification of synenkephalin-containing peptides, including a novel 23.3-kilodalton species. J Neurochem. 1987 Sep;49(3):721–728. doi: 10.1111/j.1471-4159.1987.tb00953.x. [DOI] [PubMed] [Google Scholar]
  21. Metters K. M., Rossier J., Paquin J., Chrétien M., Seidah N. G. Selective cleavage of proenkephalin-derived peptides (less than 23,300 daltons) by plasma kallikrein. J Biol Chem. 1988 Sep 5;263(25):12543–12553. [PubMed] [Google Scholar]
  22. Monstein H. J., Folkesson R., Terenius L. Proenkephalin A-like mRNA in human leukemia leukocytes and CNS-tissues. Life Sci. 1986 Dec 8;39(23):2237–2241. doi: 10.1016/0024-3205(86)90402-9. [DOI] [PubMed] [Google Scholar]
  23. Morley J. E., Kay N. E., Solomon G. F., Plotnikoff N. P. Neuropeptides: conductors of the immune orchestra. Life Sci. 1987 Aug 3;41(5):527–544. doi: 10.1016/0024-3205(87)90405-x. [DOI] [PubMed] [Google Scholar]
  24. Padrós M. R., Vindrola O., Zunszain P., Fainboin L., Finkielman S., Nahmod V. E. Mitogenic activation of the human lymphocytes induce the release of proenkephalin derived peptides. Life Sci. 1989;45(19):1805–1811. doi: 10.1016/0024-3205(89)90521-3. [DOI] [PubMed] [Google Scholar]
  25. Sibinga N. E., Goldstein A. Opioid peptides and opioid receptors in cells of the immune system. Annu Rev Immunol. 1988;6:219–249. doi: 10.1146/annurev.iy.06.040188.001251. [DOI] [PubMed] [Google Scholar]
  26. Stein C., Millan M. J., Shippenberg T. S., Peter K., Herz A. Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors. J Pharmacol Exp Ther. 1989 Mar;248(3):1269–1275. [PubMed] [Google Scholar]
  27. Vindrola O., Asai M., Zubieta M., Talavera E., Rodriguez E., Linares G. Pentylenetetrazol kindling produces a long-lasting elevation of IR-Met-enkephalin but not IR-Leu-enkephalin in rat brain. Brain Res. 1984 Apr 9;297(1):121–125. doi: 10.1016/0006-8993(84)90548-1. [DOI] [PubMed] [Google Scholar]
  28. Vindrola O., Ase A., Finkielman S., Nahmod V. E. Differential release of enkephalin and enkephalin-containing peptides from perfused cat adrenal glands. J Neurochem. 1988 Feb;50(2):424–430. doi: 10.1111/j.1471-4159.1988.tb02929.x. [DOI] [PubMed] [Google Scholar]
  29. Watson J. D., Varley J. G., Tomlin S. J., Medbak S., Rees L. H., Hinds C. J. Biochemical characterization of circulating Met-enkephalins in canine endotoxin shock. J Endocrinol. 1986 Nov;111(2):329–334. doi: 10.1677/joe.0.1110329. [DOI] [PubMed] [Google Scholar]
  30. Yoshikawa K., Aizawa T. Enkephalin precursor gene expression in postmeiotic germ cells. Biochem Biophys Res Commun. 1988 Mar 15;151(2):664–671. doi: 10.1016/s0006-291x(88)80332-2. [DOI] [PubMed] [Google Scholar]
  31. Zurawski G., Benedik M., Kamb B. J., Abrams J. S., Zurawski S. M., Lee F. D. Activation of mouse T-helper cells induces abundant preproenkephalin mRNA synthesis. Science. 1986 May 9;232(4751):772–775. doi: 10.1126/science.2938259. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES