Abstract
Regulated expression of peptidases represents a potentially powerful mechanism for regulating neurologic and immune system responses to opioid peptides1-3. Endorphins and enkephalins are naturally occurring opioid peptides, derived from processing of the precursors proopiomelanocortin (POMC) and proenkephalin, respectively4 and are thought to mediate intercellular regulatory signals during neuroimmune communication and between immune system cells5-7, β-endorphin is produced by macrophages8-10 and lymphocytes11 and modulates leukocyte function through both opioid12,13 and non-opioid peptide receptors14,15. In previous studies we have characterized a β-endorphin endopeptidase generating γ-endorphin that is expressed jn EL4 cells and is induced in murine spleen CD4+ and CD8+ T cells upon activation with immobilized anti-CD316. This enzyme has recently been purified from EL4 cells and found to have amino acid sequence and a molecular weight identical to that of insulin degrading enzyme17. This enzyme can potentially regulate β-endorphin action both by modifying the levels of β-endorphin available for receptor binding and by generating known physiologically active β-endorphin metabolites.
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References
Davis TP, Konings PN: Peptidases in the CNS: formation of biologically active, receptor-specific peptide fragments. Critical Reviews in Neurobiology 7:163, 1993
Hersh LB, Mckelvy JF: An aminopeptidase from bovine brain which catalyses the hydrolysis of enkephalin. J Neurochem 36:171, 1981
Hersh LB: Solubilization and characterization of two rat brain aminopeptidases active on Met-enkephalin. Biochemistry 20:2345, 1981
Akil H, Bronstein D, Mansour A: Overview of the endogenous opioid systems: anatomical, biochemical and functional issues. In Rodgers RJ, Cooper SJ (eds): Endorphins, Opiates and Behavioral Processes. Chichester, NY, Wiley, 1988, pp. 1
Sibinga NE, Goldstein A: Opioid peptides and opioid receptors in cells of the immune system. Annual Review of Immunology 6:219, 1988
Bhargava HN: Opioid peptides, receptors, and immune function. NIDA Research Monograph 96:220, 1990
Teschemacher H, Koch G, Scheffler H, Hildebrand A, Brantl V: Opioid peptides. Immunological significance? Annals of the New York Academy of Sciences 594:66, 1990
Lolait SJ, Lim AT, Toh BH, Funder JW: Immunoreactive beta-endorphin in a subpopulation of mouse spleen macrophages. Journal of Clinical Investigation 73:277, 1984
Lolait SJ, Clements JA, Markwick AJ, Cheng C, McNally M, Smith AI, Funder JW: Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages. Journal of Clinical Investigation 77:1776, 1986
Mechanick JI, Levin N, Roberts JL, Autelitano DJ: Proopiomelanocortin gene expression in a distinct population of rat spleen and lung leukocytes. Endocrinology 131:518, 1992
Kavelaars A, Ballieux RE, Heijnen CJ: The role of IL-1 in the corticotropin-releasing factor and arginine-vasopressin-induced secretion of immunoreactive beta-endorphin by human peripheral blood mononuclear cells. Journal of Immunology 142:2338, 1989
Szabo I, Rojavin M, Bussiere JL, Eisenstein TK, Adler MW, Rogers TJ: Suppression of peritoneal macrophage phagocytosis of Candida albicans by opioids. Journal of Pharmacology & Experimental Therapeutics 267:703, 1993
Sedqi M, Roy S, Ramakrishnan S, Elde R, Loh HH: Complementary DNA cloning of a mu-opioid receptor from rat peritoneal macrophages. Biochemical & Biophysical Research Communications 209:563, 1995
Hazum E, Chang KJ, Cuatrecasas P: Specific nonopiate receptors for beta-endorphin. Science 205:1033, 1979
Gelfand RA, Wepsic HT, Parker LN, Jadus MR: Prostaglandin E2 induces up-regulation of murine macrophage beta-endorphin receptors. Immunology Letters 45:143, 1995
Miller BC, Thiele D, Hersh LB, Cottam GL: A secreted peptidase involved in T cell B-endorphin metabolism. Immunopharmacol 31:151, 1996
Safavi A, Miller BC, Cottam L, Hersh LB: Identification of gamma-endorphin-generating enzyme as insulin-degrading enzyme. Biochemistry 35:14318, 1996
Laouar A, Wietzerbin J, Bauvois B: Divergent regulation of cell surface protease expression in HL-60 cells differentiated into macrophages with granulocyte macrophage colony stimulating factor or neutrophils with retinoic acid. International Immunology 5:965, 1993
Welgus HG, Senior RM, Parks WC, Kahn AJ, Ley TJ, Shapiro SD, Campbell EJ: Neutral proteinase expression by human mononuclear phagocytes: a prominent role of cellular differentiation. Matrix Supplement 1:363, 1992
Geppert TD, Lipsky PE: Accessory cell independent proliferation of human T4 cells stimulated by immobilized monoclonal antibodies to CD3. J Immunol 138:1660, 1987
Coligan JE, Kruisbeek AM, Margulies DH, Shevach EM, Strober W: Macrophages and Monocytes: Current Protocols in Immunology, vol. 2. New York, Wiley, 1994, p Chapter 14
Shii K, Roth RA: Inhibition of insulin degradation by hepatoma cells after microinjection of monoclonal antibodies to a specific cytosolic protease. Proceedings of the National Academy of Sciences of the United States of America 83:4147, 1986
Look AT, Ashmun RA, Shapiro LH, Peiper SC: Human myeloid plasma membrane glycoprotein CD13 (gpl50) is identical to aminopeptidase N. Journal of Clinical Investigation 83:1299, 1989
Letarte M, Vera S, Tran R, Addis JB, Onizuka RJ, Quackenbush EJ, Jongeneel CV, Mclnnes RR: Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase. Journal of Experimental Medicine 168:1247, 1988
Vincent B, Beaudet A, Dauch P, Vincent JP, Checler F: Distinct properties of neuronal and astrocytic endopeptidase 3.4.24.16: a study on differentiation, subcellular distribution, and secretion processes. Journal of Neuroscience 16:5049, 1996
Schweigerer L, Schmidt W, Teschemacher H, Gramsch C: beta-Endorphin: surface binding and internalization in thymoma cells. Proceedings of the National Academy of Sciences of the United States of America 82:5751, 1985
Falke NE, Fischer EG: Opiate receptor mediated internalization of 1251-beta-endorphin in human polymorphonuclear leucocytes. Cell Biology International Reports 10:429, 1986
Kuo WL, Gehm BD, Rosner MR, Li W, Keller G: Inducible expression and cellular localization of insulindegrading enzyme in a stably transfected cell line. Journal of Biological Chemistry 269:22599, 1994
Authier F, Rachubinski RA, Posner BI, Bergeron JJ: Endosomal proteolysis of insulin by an acidic thiol metalloprotease unrelated to insulin degrading enzyme. Journal of Biological Chemistry 269:3010, 1994
Authier F, Posner BI, Bergeron JJ: Insulin-degrading enzyme. Clinical & Investigative Medicine-Medecine Clinique et Experimentale 19:149, 1996
Heijnen CJ, Kavelaars A, Ballieux RE: Beta-endorphin: cytokine and neuropeptide. Immunological Reviews 119:41, 1991
Hemmick LM, Bidlack JM: Beta-endorphin stimulates rat T lymphocyte proliferation. Journal of Neuroimmunology 29:239, 1990
van den Bergh P, Rozing J, Nagelkerken L: Two opposing modes of action of beta-endorphin on lymphocyte function. Immunology 72:537, 1991
van den Bergh P, Rozing J, Nagelkerken L: Identification of two moieties of beta-endorphin with opposing effects on rat T-cell proliferation. Immunology 79:18, 1993
Hagi K, Inaba K, Sakuta H, Muramatsu S: Enhancement of murine bone marrow macrophage differentiation by beta-endorphin. Blood 86:1316, 1995
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Thiele, D.L., Sarada, B., Dang, T., Safavi, A., Hersh, L.B., Cottam, G.L. (1998). Regulated Expression of an Endopeptidase that Hydrolyses β-Endorphin During Differentiation of Macrophages and T Cells. In: Friedman, H., Madden, J.J., Klein, T.W. (eds) Drugs of Abuse, Immunomodulation, and Aids. Advances in Experimental Medicine and Biology, vol 437. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5347-2_32
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DOI: https://doi.org/10.1007/978-1-4615-5347-2_32
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