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. 1989 Feb;83(2):733–737. doi: 10.1172/JCI113940

Expression of pro-opiomelanocortin gene and quantification of adrenocorticotropic hormone-like immunoreactivity in human normal peripheral mononuclear cells and lymphoid and myeloid malignancies.

R Buzzetti 1, L McLoughlin 1, P M Lavender 1, A J Clark 1, L H Rees 1
PMCID: PMC303737  PMID: 2536407

Abstract

Using Northern blotting with a human genomic DNA probe for the pro-opiomelanocortin (POMC) gene, we have shown specific mRNA in normal human peripheral mononuclear cells (PBMC); the presence of specific mRNA was also observed in a T lymphocyte cell line derived from a patient with lymphoma. We then demonstrated that PBMC translate the message into protein. Thus, using a radioimmunoassay with an antibody for ACTH, a median of 29 pg of ACTH-like immunoreactivity (ACTH-LIR) was found in 10(7) PBMC. ACTH-LIR was also detected in seven different cell lines derived from patients with lymphoid and myeloid malignancies, two of them JM and U937 showing the highest values 135 and 108 pg/10(7) cells, respectively. The chromatographic characterization of this ACTH-LIR showed, at least, three molecular forms of immunoreactive ACTH with molecular weights of the order of 31,000 POMC, 22,000 ACTH, and 4,500 ACTH, in addition to high-molecular-weight material (greater than 43,000). We conclude that PBMC produce ACTH-LIR which may act as a paracrine immunomodulator in a similar way to lymphokines and/or may signal the adrenal gland to secrete glucocorticoids.

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Selected References

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  1. Alvarez-Mon M., Kehrl J. H., Fauci A. S. A potential role for adrenocorticotropin in regulating human B lymphocyte functions. J Immunol. 1985 Dec;135(6):3823–3826. [PubMed] [Google Scholar]
  2. Bohs C. T., Fish J. C., Miller T. H., Traber D. L. Pulmonary vascular response to endotoxin in normal and lymphocyte depleted sheep. Circ Shock. 1979;6(1):13–21. [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Civelli O., Birnberg N., Herbert E. Detection and quantitation of pro-opiomelanocortin mRNA in pituitary and brain tissues from different species. J Biol Chem. 1982 Jun 25;257(12):6783–6787. [PubMed] [Google Scholar]
  5. Cochet M., Chang A. C., Cohen S. N. Characterization of the structural gene and putative 5'-regulatory sequences for human proopiomelanocortin. Nature. 1982 May 27;297(5864):335–339. doi: 10.1038/297335a0. [DOI] [PubMed] [Google Scholar]
  6. DeBold C. R., Menefee J. K., Nicholson W. E., Orth D. N. Proopiomelanocortin gene is expressed in many normal human tissues and in tumors not associated with ectopic adrenocorticotropin syndrome. Mol Endocrinol. 1988 Sep;2(9):862–870. doi: 10.1210/mend-2-9-862. [DOI] [PubMed] [Google Scholar]
  7. DuPont A. G., Somers G., Van Steirteghem A. C., Warson F., Vanhaelst L. Ectopic adrenocorticotropin production: disappearance after removal of inflammatory tissue. J Clin Endocrinol Metab. 1984 Apr;58(4):654–658. doi: 10.1210/jcem-58-4-654. [DOI] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Harbour-McMenamin D., Smith E. M., Blalock J. E. Bacterial lipopolysaccharide induction of leukocyte-derived corticotropin and endorphins. Infect Immun. 1985 Jun;48(3):813–817. doi: 10.1128/iai.48.3.813-817.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Imura H. Ectopic hormone syndromes. Clin Endocrinol Metab. 1980 Jul;9(2):235–260. doi: 10.1016/s0300-595x(80)80032-6. [DOI] [PubMed] [Google Scholar]
  11. Johnson H. M., Smith E. M., Torres B. A., Blalock J. E. Regulation of the in vitro antibody response by neuroendocrine hormones. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4171–4174. doi: 10.1073/pnas.79.13.4171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koff W. C., Dunegan M. A. Modulation of macrophage-mediated tumoricidal activity by neuropeptides and neurohormones. J Immunol. 1985 Jul;135(1):350–354. [PubMed] [Google Scholar]
  13. Lacaze-Masmonteil T., de Keyzer Y., Luton J. P., Kahn A., Bertagna X. Characterization of proopiomelanocortin transcripts in human nonpituitary tissues. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7261–7265. doi: 10.1073/pnas.84.20.7261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lolait S. J., Clements J. A., Markwick A. J., Cheng C., McNally M., Smith A. I., Funder J. W. Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages. J Clin Invest. 1986 Jun;77(6):1776–1779. doi: 10.1172/JCI112501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lolait S. J., Lim A. T., Toh B. H., Funder J. W. Immunoreactive beta-endorphin in a subpopulation of mouse spleen macrophages. J Clin Invest. 1984 Jan;73(1):277–280. doi: 10.1172/JCI111203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Oates E. L., Allaway G. P., Armstrong G. R., Boyajian R. A., Kehrl J. H., Prabhakar B. S. Human lymphocytes produce pro-opiomelanocortin gene-related transcripts. Effects of lymphotropic viruses. J Biol Chem. 1988 Jul 25;263(21):10041–10044. [PubMed] [Google Scholar]
  17. Pflüger K. H., Gramse M., Gropp C., Havemann K. Ectopic ACTH production with autoantibody formation in a patient with acute myeloblastic leukemia. N Engl J Med. 1981 Dec 31;305(27):1632–1636. doi: 10.1056/NEJM198112313052706. [DOI] [PubMed] [Google Scholar]
  18. Ratter S. J., Lowry P. J., Besser G. M., Rees L. H. Chromatographic characterization of adsrenocorticotrophin in human plasma. J Endocrinol. 1980 Jun;85(3):359–369. doi: 10.1677/joe.0.0850359. [DOI] [PubMed] [Google Scholar]
  19. Rees L. H., Cook D. M., Kendall J. W., Allen C. F., Kramer R. M., Ratcliffe J. G., Knight R. A. A radioimmunoassay for rat plasma ACTH. Endocrinology. 1971 Jul;89(1):254–261. doi: 10.1210/endo-89-1-254. [DOI] [PubMed] [Google Scholar]
  20. Smith E. M., Blalock J. E. Human lymphocyte production of corticotropin and endorphin-like substances: association with leukocyte interferon. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7530–7534. doi: 10.1073/pnas.78.12.7530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith E. M., Brosnan P., Meyer W. J., Blalock J. E. An ACTH receptor on human mononuclear leukocytes. Relation to adrenal ACTH-receptor activity. N Engl J Med. 1987 Nov 12;317(20):1266–1269. doi: 10.1056/NEJM198711123172006. [DOI] [PubMed] [Google Scholar]
  22. Smith E. M., Morrill A. C., Meyer W. J., 3rd, Blalock J. E. Corticotropin releasing factor induction of leukocyte-derived immunoreactive ACTH and endorphins. 1986 Jun 26-Jul 2Nature. 321(6073):881–882. doi: 10.1038/321881a0. [DOI] [PubMed] [Google Scholar]
  23. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Westly H. J., Kleiss A. J., Kelley K. W., Wong P. K., Yuen P. H. Newcastle disease virus-infected splenocytes express the proopiomelanocortin gene. J Exp Med. 1986 Jun 1;163(6):1589–1594. doi: 10.1084/jem.163.6.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]

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