2003, Número 1-2
<< Anterior Siguiente >>
Microbiología 2003; 45 (1-2)
Quimiotaxis de leucocitos humanos y de rata por el opioide no-peptídico, delta-selectivo SNC 80
Ordaz-Sánchez I, Weber RJ, Rice KC, Zhang X, Padilla RC, Tamez-Guerra R, Méndez-Vázquez JL, Gómez-Flores R
Idioma: Ingles.
Referencias bibliográficas: 49
Paginas: 16-23
Archivo PDF: 91.55 Kb.
RESUMEN
Opioides como la morfina, representan la principal fuente de alivio para la mayor
parte de los casos de dolor crónico no maligno, moderado o severo. Sin
embargo, el abuso de opioides puede llevar a padecer de infecciones tales como
la hepatitis y el SIDA, debido a que estas sustancias se han asociado con la supresión
de varios parámetros de función inmune incluyendo a la resistencia
antimicrobiana, la producción de anticuerpos, la fagocitosis mediada por
monocitos/macrófagos, y la quimiotaxis de neutrófilos y monocitos.
Nosotros hemos reportado previamente las propiedades inmunopotenciadoras de agonistas
y antagonistas selectivos de receptores de opioides no peptídicos. En el
presente estudio, se evaluaron los efectos del agonista opioide no peptídico
del tipo delta (+)-4-((alfa R)-alfa-((2S, 5R)-4-alil-2, 5-dimetil-1-piperazinil)-3-metoxibenzil)-N,
N-dietil-benzamiae (SNC 80) en la quimiotaxis de linfocitos tímicos de
rata y de células mononucleares de sangre periférica humana, utilizando
una cámara de Wilkinson modificada. Se observó que el SNC 80 a las
concentraciones de 10
-10,10
-9,10
-8,10
-7,
y 10
-6 M, estimuló significativamente
(
p ‹ 0.01) la quimiotaxis (demostrado mediante pruebas de tablero) de
linfocitos tímicos de rata (1.3,1.55,1.58,1.75, y 1.8 veces de incremento
respectivamente) y leucocitos humanos (1.13,1.37,1.43,1.7, y 1.83 veces de incremento
respectivamente) comparado con el control sin tratar. Los efectos del SNC 80 sobre
la quimiotaxis de leucocitos de rata y humanos se antagonizaron con el uso de
naloxona, indicando que la modulación de la quimiotaxis inducida por este
opioide es a través de un receptor clásico de opioides. El desarrollo
y uso de opioides no peptídicos como el SNC 80 podrían tener un
impacto inmediato no sólo como analgésicos potentes, sino en inmunorregulación.
REFERENCIAS (EN ESTE ARTÍCULO)
Ader, R., N. Cohen & D.L. Felten. 1985. Brain, behavior, and immunity. Brain Behav. Immun. 1:1-6.
Arora, P.K., E. Fride, J. Petitto, K. Waggie & P. Skolnick. 1990. Morphine-induced immune alterations in vivo. Cell Immunol. 126: 343-353.
Bilsky, E.J., S.N. Calderon, T. Wang, R.N. Bernstein, P. Davis, V.J. Hruby, R.W. McNutt, R.B. Rothman, K.C. Rice & F. Porreca. 1995. SNC 80, a selective, nonpeptidic and systemically active opioid delta agonist. J. Pharmacol. Exp. Ther. 273:359-366.
Calderon, S.N., R.B. Rothman, F. Porreca, J.L. Flippen-Anderson, R.W. McNutt, H. Xu, L.E. Smith, E.J. Bilsky, P. Davis & K.C. Rice. 1994. Probes for narcotic receptor mediated phenomena. 19. Synthesis of (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- methoxybenzyl]-N,N-diethylbenzamide (SNC 80): a highly selective, nonpeptide delta opioid receptor agonist. J. Med. Chem. 37:2125-8.
Chen, T., E. Scott & D.C. Morrison. 1994. Differential effects of serum on lipopolysaccharide receptor-directed macrophage activation for nitric oxide production. Immunol. Lett. 40:179-87.
Choi Y., L.F. Chuang, K.M. Lam, H.F. Kung, J.M. Wang, B.I. Osburn & R.Y. Chuang. 1999. Inhibition of chemokine-induced chemotaxis of monkey leukocytes by mu-opioid receptor agonists. In Vivo. 13:389-96.
Chung, C.Y., S. Funamoto & R.A. Firtel. 2001. Signaling pathways controlling cell polarity and chemotaxis. Trends Bioch. Sci. 26:557-66.
Gomez-Flores R., C. Rodríguez-Padilla & R. Tamez-Guerra. 1990. Early production of a chemotactic factor to T lymphocytes by peritoneal macrophages. Cell. Immunol. 126:1-15.
Gómez-Flores, R., S. Gupta, R. Tamez-Guerra & R.T. Mehta. 1995. Determination of MICs for Mycobacterium avium-M. intracellulare complex in liquid medium by a colorimetric method. J. Clin. Microbiol. 33:1842-1846.
Gómez-Flores, R., S. D. Tucker, R. Kansal, R. Tamez-Guerra & R. T. Mehta. 1997. Enhancement of antibacterial activity of clofazimine against Mycobacterium avium-M. intracellulare complex infection induced by IFN-g is mediated by TNF-a. J. Antimicrob. Chemother. 39:189-197.
Gomez-Flores, R. & R.J. Weber. 1999. Opioids, opioid receptors, and the immune system, pp. 281-314. In N. Plotnikoff, R. Faith, A. Murgo and R. Good (Eds). Cytokines-Stress and Immunity. Boca Raton: CRC Press.
Gomez-Flores R. & R.J. Weber. 2001. Increased tumor necrosis factor-a and nitric oxide production by rat macrophages following in vitro stimulation and intravenous administration of the d-opioid agonist SNC 80. Life Sci 68:2675-84.
Grimm, M.C., A. Ben-Baruch, D.D. Taub, O.M. Howard, J.M. Wang & J.J. Oppenheim. 1998. Opiate inhibition of chemokine-induced chemotaxis. Ann. N.Y. Acad. Sci. 840:9-20.
Hambrook, J.M., B.A. Morgan, M.J. Rance & C.F. Smith. 1976. Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates. Nature 262:782-783.
Haverkos, H.W. 1987. Factors associated with the pathogenesis of AIDS. J. Infect. Dis. 156:251-7.
Hofbauer, R., D. Moser, H. Salfinger, M. Frass & S. Kapiotis. 1998. Sufentanil inhibits migration of human leukocytes through human endothelial cell monolayers. Anesth. Analg. 87:1181-5.
Hu, S., C.C. Chao, C.C. Hegg, S. Thayer & P.K. Peterson. 2000. Morphine inhibits human microglial cell production of, and migration towards, RANTES. J. Psychopharmacol. 14:238-43.
Ishikawa, M., K. Tanno, A. Kamo, Y. Takayanagi & K. Sasaki. 1993. Enhancement of tumor growth by morphine and its possible mechanism in mice. Biol. Pharmacol. Bull. 16:762-6.
Kaldjian, E.P., G.H. Chen & K.B. Cease. 1992. Enhancement of lymphocyte proliferation assays by use of serum-free medium. J. Immunol. Methods 147:189-95.
Kamada, H., Y. Tsutsumi, Y. Yamamoto, T. Kihira, Y. Kaneda, Y. Mu, H. Kodaira, S.-I. Tsunoda, S. Nakagawa & T. Mayumi. 2000. Antitumor activity of tumor necrosis factor-alpha conjugated with polyvinylpyrrolidone on solid tumors in mice. Cancer Res. 60:6416-6420.
Kaneider, N.C., C.M. Reinisch, S. Dunzendorfer, J. Romisch & C.J. Wiedermann. 2002. Syndecan-4 mediates antithrombin-induced chemotaxis of human peripheral blood lymphocytes and monocytes. J. Cell Sci. 115:227-36.
Kansal, R., R. Gomez-Flores & R.T. Mehta. 1997. Therapeutic efficacy of liposomal clofazimine against Mycobacterium avium complex (MAC) in mice depends on size of initial inoculum and duration of infection. Antimicrob. Agents Chemother. 41:17-23.
Kaplan, A.P. 2001. Chemokines, chemokine receptors and allergy. Int. Arch. Allergy Immunol. 124:423-31.
Klimp, A.H., E.G. de Vries, G.L. Scherphof & T. Daemen. 2002. A potential role of macrophage activation in the treatment of cancer. Crit. Rev. Oncol. Hematol. 44:143-161.
Kuijpers, T.W., R.A. Van Lier, D. Hamann, M. de Boer, L.Y. Thung, R.S. Weening, A.J. Verhoeven & D. Roos. 1997. Leukocyte adhesion deficiency type 1 (LAD-1)/variant. A novel immunodeficiency syndrome characterized by dysfunctional beta2 integrins. J. Clin. Investigat. 100:1725-33.
Liu, Y., D.J. Blackbourn, L.F. Chuang, K.F. Killam Jr. & R.Y. Chuang. 1992. Effects of in vivo and in vitro administration of morphine sulfate upon rhesus macaque polymorphonuclear cell phagocytosis and chemotaxis. J. Pharmacol. Exp. Ther. 263:533-9.
Lysle, D.T., M.E. Coussons, V.J. Watts, E.H. Bennett & L.A. Dykstra. 1993. Morphine-induced alterations of immune status: dose dependency, compartment specificity and antagonism by naltrexone. J. Pharmacol. Exp. Ther. 265:1071-1078.
Makman, M.H., T.V. Bilfinger & G.B. Stefano. 1995. Human granulocytes contain an opiate alkaloid-selective receptor mediating inhibition of cytokine-induced activation and chemotaxis. J. Immunol. 154:1323-30.
Matzner, Y. 1987. Neutrophil function studies in clinical medicine. Transf. Med. Rev 1:171-81.
Miyagi, T., L.F. Chuang, K.M. Lam, H. Kung, J.M. Wang, B.I. Osburn & R.Y. Chuang. 2000. Opioids suppress chemokine-mediated migration of monkey neutrophils and monocytes - an instant response. Immunopharmacology 47:53-62.
Negus, S.S., M.B. Gatch, N.K. Mello, X. Zhang & K.C. Rice. 1998. Behavioral effects of the delta-selective opioid agonist SNC80 and related compounds in rhesus monkeys. J. Pharmacol. Exp. Ther. 286:362-75.
Ni, X., K.R. Gritman, T.K. Eisenstein, M.W. Adler, K.E. Arfor & R.F. Tuma. 2000. Morphine attenuates leukocyte/endothelial interactions. Microvasc. Res. 60:121-30.
Nowak, J.E., R. Gomez-Flores, S.N. Calderon, K.C. Rice & R.J. Weber. 1998. Rat NK cell, T cell, and macrophage functions following intracerebroventricular injection of SNC 80. J. Pharmacol. Exp. Ther. 286:931-937.
Pacl, D.S. 2001. Managing the pain of advanced chronic disease. Tex. Med. 97:38-41.
Pasnik, J., H. Tchorzewski, Z. Baj, M. Luciak & M. Tchorzewski. 1999. Priming effect of met-enkephalin and beta-endorphin on chemiluminescence, chemotaxis and CD11b molecule expression on human neutrophils in vitro. Immunol. Lett. 67:77-83.
Passik, S.D. & H.J. Weinreb. 2000. Managing chronic nonmalignant pain: overcoming obstacles to the use of opioids. Adv. Ther. 17:70-83.
Perez-Castrillon, J.L., J.L. Perez-Arellano, J.D. Garcia-Palomo, A. Jimenez-Lopez & S. De Castro. 1992. Opioids depress in vitro human monocyte chemotaxis. Immunopharmacology 23:57-61.
Pitrak, D.L. 1999. Neutrophil deficiency and dysfunction in HIV-infected patients. Am. J. Health Syst. Pharmacol. 56:S9-16.
Rogers, T.J., A.D. Steele, O.M. Howard & J.J. Oppenheim. 2000. Bidirectional heterologous desensitization of opioid and chemokine receptors. Ann. N.Y. Acad. Sci. 917:19-28.
Sharp, B.M., K. McAllen, G. Gekker, N.A. Shahabi & P.K. Peterson. 2001. Immunofluorescence detection of delta opioid receptors (DOR) on human peripheral blood CD4+ T cells and DOR-dependent suppression of HIV-1 expression. J. Immunol. 167:1097-102.
Szabo, I., X.H. Chen, L. Xin, M.W. Adler, O.M. Howard, J.J. Oppenheim & T.J. Rogers. 2002. Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain. Proc. Natl. Acad. Sci. U S A. 99:10276-81.
Taub, D.D. & J.J. Oppenheim. 1994. Chemokines, inflammation and the immune system. Ther. Immunol. 1:229-46.
Watson, R.R., R.H. Prabhala, H.R. Darban, M.D. Yahya & T.L. Smith. 1988. Changes in lymphocyte and macrophage subsets due to morphine and ethanol treatment during a retrovirus infection causing murine AIDS. Life Sci. 43: v-xi.
Weber, R.J., L.C. Band, B. de Costa, A. Pert & K.C. Rice. 1991. Neural control of immune function: Opioids, opioid receptors, and immunosuppression. NIDA Res. Monograph Series 105: 96-102.
Wilkinson, P.C. & I.C. McKay. 1971. The chemotactic activity of native and denatured serum albumin. Int. Arch. Allergy Appl. Immunol. 41:237-47.
Wilkinson, C.A. 1975. Leucocyte locomotion and chemotaxis. The influence of divalent cations and cation ionophores. Exp. Cell Res. 93:420-6.
Wilkinson, P.C., M. Komai-Koma & I. Newman. 1997. Locomotion and chemotaxis of lymphocytes. Autoimmunity 26(1):55-72.
Zhang, N., D. Hodge, T.J. Rogers & J.J. Oppenheim. 2003. Ca2+-independent protein kinase Cs mediate heterologous desensitization of leukocyte chemokine receptors by opioid receptors. J. Biol. Chem. 278:12729-12736.
Zigmond, S.H. and J.G. Hirsch. 1973. Leukocyte locomotion and chemotaxis. New method for evaluation, and demonstration of a cell-derived chemotactic factor. J. Exp. Med. 137:387-410.