Heroin is a well known opioid that causes al-terations to the immune system of a number of investigated animals. Only a few studies have explored the effect of heroin on the lymphocytes maturation. Thymocyte progenitors originate from haematopoietic stem cells in the bone marrow. The immature T-cells express neither CD4 nor CD8, and are therefore classed as double-negative (CD4-CD8-) cells. CD34 glycoprotein is the only defined marker of the immature T-lymphocytes. In this study we have investigated the changes induced in CD34+ rat thymocytes after heroin administration by immunofluores-cence in frozen rat thymus sections using the 4H11 monoclonal anti-CD34 antibody. There is a remarkable decrease in the number of CD34+ immature thymocytes when examined 1hour after last heroin injection and a small recover when examination took place 20 days after last injection. The above results suggest a major effect of heroin administration early in the ma- turation process of T lymphocytes probably by increasing the apoptotic cell death and the ne- gative consequences for the immune system responses.
KeywordsHeroinRat ThymusCD34
Vizi, E.S., Orsó, E., Osipenko, O.N., Haskó, G. and Elenkov, I.J. (1995) Neurochemical, electrophysiological and immunocytochemical evidence for a noradrenergic link between the sympathetic nervous system and thy-mocytes, Neuroscience, 68(4), 1263-1276.
Klous, M.G., Van den Brink, W., Van Ree, J.M. and Bei-jnen, J.H. (2005) Development of pharmaceutical heroin preparations for medical co-prescription to opioid de-pendent patients. Drug Alcohol Depend, 80(3), 283-295.
Mahajan, S.D., Schwartz, S.A., Aalinkeel, R., Chawda, R.P., Sykes, D.E. and Nair, M.P. (2005) Morphine modu-lates chemokine gene regulation in normal human astro-cytes. Clinical Immunology, 115(3), 323-332.
Vallejo, R., de Leon-Casasola, O. and Benyamin, R. (2004) Opioid therapy and immunosuppression: A review American Journal of Therapeutics, 11(5), 354-365.
Friedman, H. and Eisenstein, T.K. (2004) Neurological basis of drug dependence and its effects on the immune system. Journal of Neuroimmunology, 147(1-2), 106- 108.
Clouet, D. and Rather, M. (1979) Catecholamine biosyn-thesis in brains of rats treated with morphine. Science, 168(3), 854-856.
Lysle, D.T., Coussons, M.E., Watts, V.J., Bennett, E.H. and Dykstra, L.A. (1993) Morphine-induced alterations of immune status: Dose dependency, compartment speci-ficity and antagonism by naltrexone. Journalof Phar- macology and Experimental Therapeutics, 265(3), 1071- 1078.
Bryant, H.U. and Roudebush, R.E. (1990) Suppressive effects of morphine pellet implants on in vivo parameters of immune function. Journalof Pharmacology and Ex- perimental Therapeutics, 255(2), 410-414.
Lockwood, L.L., Silbert, L.H., Fleshner, M., Laudenslager, M.L., Watkins, L.R. and Maier, S.F. (1994) Morphine- Induced decreases in in vivo antibody responses. Brain, Behavior and Immunity, 8(1), 24-36.
Haddad, R., Guimiot, F., Six, E., Jourquin, F., Setterblad, N., Kahn, E., Yagello, M., Schiffer, C., Andre-Schmutz, I., Cavazzana-Calvo, M., Gluckman, J.C., Delezoide, A.L., Pflumio, F. and Canque, B. (2006). Dynamics of thymus-colonizing cells during human development. Immunity, 24(2), 217-230.
Nelson, C.J., How, T. and Lysle, D.T. (1999) Enhance-ment of the contact hypersensitivity reaction by acute morphine administration rat the elicitation phase. Clini-cal Immunology, 93(2), 176-183.
Miller, J.F. (1996) Uncovering thymus functions. Per- spectives in Biology and Medicine, 39(3), 338-352.
Chang, S.J., Huang, T.S., Wang, K.L., Wang, T.Y., Yang, Y.C., Chang, M.D., Wu, Y.H. and Wang, H.W. (2008) Genetic network analysis of human CD34+ hematopoietic stem/precursor cells. Taiwanese Journal of Obstetrics and Gynecology, 47(4), 422-430.
Porada, C.D., Harrison-Findik, D.D., Sanada, C., Vali-ente, V., Thain, D. and Simmons, P.J. (2008) Almeida- Porada G, Zanjani ED. Development and characterization of a novel CD34 monoclonal antibody that identifies sheep hematopoietic stem/progenitor cells. Experimental Hematology, 36(12), 1739-1749.
Engelhardt, M., Lübbert, M. and Guo, Y. (2002) CD34(+) or CD34(-): Which is the more primitive? Leukemia, 16(9), 1603-1608.
Tegeder, I., Grosch, S., Schmidtko, A., Haussler, A., Sch- midt, H., Niederberger, E, Scholich, K. and Geisslinger, G. (2003) G protein-independent G(1) cell cycle block and apoptosis with morphine in adenocarcinoma cells: Involvement of p53 phosphorylation. Cancer Research, 63, 1846-1852.
Quaglino, D. and Ronchetti, I.P. (2001) Cell death in the rat thymus: A minireview Apoptosis, 6(5), 389-401.
Theodoros, K. and Burntenas, P. (1993). Immunofluo-rescence stady of astrocytes unter normal conditions and administration of heroin. Biosell, 17(2), 119-123.
Tegeder, I. and Geisslinger, G. (2004) Opioids as modula-tors of cell death and survival—unraveling mechanisms and revealing new indications Pharmacological Reviews, 56(3), 351-369.
Golstain, M., Freedman, L. and Backstrom, T. (1970) The inhibition of catecholamine biosynthesis by apomorphine. Journal of Pharmacy and Pharmacology, 22(9), 715- 717.
Malev, H. and Pericid, D. (1987) Sex difference in the turnover of GABA in the rat substantia nigra. Journal of Neural Transmission, 70(3-4), 321-328.
Haynes, B.F., Denning, S.M., Singer, K.H. and Kurtzberg, J. (1989) Ontogeny of cell precursors: A model for the initial stages of human T-cell development. Journal of Immunology Today, 10(3), 87.
Spits, H.C. (1994) Early stages in human and mouse T-cell development. Current Opinion in Immunology, 6(2), 212.
Toribio, M.L., Martinez, A.C., Marcos, M.A.R., Marquez, C., Cabrero, E. and de la Hera, A. (1986) A role for T3+4-6-8-transitional thymocytes in the differentiation of mature and functional T cells from human prothymocytes. Proceedings of the National Academy of Sciences, 83, 6985.
Toribio, M.L., de la Hera, A., Borst, J., Marcos, M.A.R., Marquez, C., Alonso, J.M., Barccna, A. and Martinez, A. (1988) Involvement of the interleukin 2 pathway in the rearrangement and expression of both alpha/beta and gamma/delta T cell receptor genes in human T cell pre-cursors. Journal of Experimental Medicine, 168(6), 2231.
Hari, T. and Spits, H. (1991) Clonal analysis of human CD4-CD8-CD3-thymocytes highly purified from postnatal thymus. Journal of Immunology, 146(7), 2116.
Sanchez, M.J., Spits, H., Lanier, L.L. and Phillips, J.H. (1993) Human natural killer cell committed thymocytes and their relation to the T cell lineage. Journal of Ex-perimental Medicine, 178(6), 1857-1866.
Galy, A., Barcena, A., Verma, S. and Spits, H. (1993) Precursors of CD3 + CD4 + CD8 + cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development. Journal of Experimental Medicine, 178(2), 391-401.
Poggi, A., Costa, P., Morelli, L., Cantoni, C., Pella, N., Spada, F., Biassoni, R., Nanni, L., Revello, V., Tomasello, E., Mingari, M.C., Moretta, A. and Moretta, L. (1996). Expression of human NKRP1A by CD34+ immature thymocytes: NKRP1A-mediated regulation of prolifera-tion and cytolytic activity, European Journal of Immu-nology, 26(6), 1266-1272.
Stoll-Keller, F., Schmitt, C., Thumann, C., Schmitt, M.P., Caussin, C. and Kirn, A. (1997) Effects of morphine on purified human blood monocytes. Modifications of prop-erties involved in antiviral defences. International Jour-nal of Immunopharmacology, 19(2), 95-100.
Elknerová, K., Lacinová, Z., Soucek, J., Marinov, I. and St?ckbauer, P. (2007) Growth inhibitory effect of the an-tibody to hematopoietic stem cell antigen CD34 in leu-kemic cell lines. Neoplasma, 54(4), 311-320.
Krauter, J., Hartl, M., Hambach, L., Kohlenberg, A. Gunsilius, E., Ganser, A. and Heil, G. (2001) Receptor- mediated endocytosis of CD34 on hematopoietic cells after stimulation with the monoclonal antibody anti- HPCA-1, Journal of Hematotherapy and Stem Cell Re-search, 10(6), 863-871.
Mao, J., Price, D.D. and Mayer, D.J. (1994) Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C. Journal of Neuroscience, 14(4), 2301-2312.
Fecho, K., Maslonek, K.A., Coussons-Read, M.E., Dykstra, L.A. and Lysle, D.T. (1994) Macrophagederived nitric oxide is involved in the depressed concanavalin A re-sponsiveness of splenic lymphocytes from rats adminis-tered morphine in vivo. Journal of Immunology, 152(12), 5845-5852.
Wu, W.R., Zheng, J.W., Li, N.. Bai, H,Q., Zhang, K.R.. and Li, Y. (1999) Immunosuppressive effects of dihydro- etorphine, a potent narcotic analgesic, in dihydroetorphine- dependent mice. European Journal of Pharmacology, 366(2-3), 61-69.
Fecho, K. and Lysle, D.T. (2000) Heroin-induced altera-tions in leukocyte numbers and apoptosis in the rat spleen. Cellular Immunology, 202(2), 113-123.
Sharp, B.M., McAllen, K., Gekker, G., Shahabi, N.A. and Peterson, P.K. (2001) Immunofluorescence detection of delta opioid receptors (DOR) on human peripheral blood CD4+ T cells and DOR-dependent suppression of HIV-1 expression. Journal of Immunology, 167(2), 1097-1102.