Action of the 4-Nitro-2-Phenoximethanesulphonanilide (Nimesulide) on Neutrophil Chemotaxis and Superoxide Production
Keywords:
neutrophil, superoxide, chemotaxis, 4-nitro-2-phenoximethanesulphonanilideAbstract
4-nitro-2-phenoximethanesulphonanilide (nimesulide) is a nonsteroidal anti-inflammatory agent that has been employed in the treatment of inflammatory diseases because of its specific actions on the inflammatory response mechanisms caused by injury. The objectives of this paper were to determine the action of this agent on two notable neutrophil functions, chemotaxis and production of the superoxide anion. These two functions were studied after the neutrophils were pre-incubated with three different concentrations of 4-nitro-2-phenoximethanesulphonanilide (0.1; 0.3 and 0.5 mN). The results obtained herein demonstrated that 4-nitro-2-phenoximethanesulphonanilide-exposed peripheral blood neutrophils from healthy subjects produced significantly less superoxide when challenged by phorbol-mirystate acetate (PMA at 50 ng/ml) or formy-methionil-leucyl-phenilalanine (FMLP 10 -7 M) and opsonizided zymozan (1 mg/ml). Additionally, the agent was equally effective in reducing the PMN chemotoaxis when challenged by C5a factor (2% zimozan activated solution), FMLP 10 -9 M and leukotrien (3. 10 -7 M). The results obtained suggest that in addition to its interference in the metabolism of the aracdonic acid, the 4-nitro-2 phenoximethanesulphonanilide may interfere in a more direct fashion with the neutrophil function. This specific action may contribute to its anti-inflammatory activity.
Downloads
References
. ABRAMSON, S.; EDELSON, H.; KAPLAN, H .; LUDEEWIG, R. & WEISSMANN, G. - Inhibition of neutrophil activation by non-steroidal anti-inflammatory drugs. Am J Med, 74: 3-6, 1984.
ANDERSON, T.; KAHIGREN, C.; LEW, P. D. & STENDAHL, O. - Cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Correlation to cahges in the cytosolic free Ca Level and action of phorbol myristate acetate. J Clin Invest, 79: 1226-1233, 1987.
BABIOR, B. M. - Owygen-dependent microbial killing by phagocytes. N Engl Med J, 298: 659-668, 1978.
BABIOR, B. M.; CURNUTTE, J. T. & MCMURRICH, B. J. - The particulate superoxideforming system from human neutrophils. Properties of the system and further evidence supporting its participation in the respiratory burst. J Clin Invest, 58: 989-996, 1976.
BABIOR, B. M.; KIPNES, R. S. & CURNUTTE, J. T. - Biological defenses mechanism. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest, 52: 741-744, 1973.
BAGGIOLINI, M. & KERNEN, P. - Neutrophil activation, control of shape change, exocytosis and respiratory burst. NIPS, 7: 215-219, 1982.
BAGGIOLINI, M.; BOULAY, F.; BADLEY, J. A. & CURNUTTE, J. T. - Activation of neutrophil leukocytes: chemoattractant receptors and respiratory burst. FASEB, 7: 1004-1010, 1993.
BATES, E. J.; LOWTHER, D. A. & HANDLEY, C. J. - Oxygen free-radicals mediate and inhibition of proteoglycan synthesis in cultured articular cartilage. Ann Rheum Dis, 43: 462-469, 1984.
BEBILACQUA,M.; VAGO, T.&BERETTA,A.-Nimesulide as an inhibitor of superoxide anion (02) production by human polymorphonuclear leukocytes. in Frontiers in gynecological series - Pain and Reproduction. A. R. GENAZZANI, G. NAPPI, F. FACCHINETTI, E. MARTIGNOMI. ed. The Parthenon publishing Group, New Jersey, USA, 265-272, 1987.
BEBILACQUA, M.; NORBIATO, G.; BALDI, G.; BERTORA, P.; VAGO, T. & CHEBAT, E. - Activation of protein kinase C by respiratory burst stimalats desensitizes beta2-adrenoreceptores on human neutrophils. Drug Invest, 3: 54-65, 1991.
BOYUM, A. -Isolation of mononuclear cells and granuloccytes from human blood. J Clin Lab Invest, 21: 77-89, 1968.
CAPSONIJ, F.; VENEGONI, E.; MINONZIO, F.; ONGARI, A. M.; MARESCA, V. & ZANUSSI, C. - Inhibition of neutrophil oxidative matabolism by Nimesulide. Agents Act, 21: 121-129, 1987.
CARR, D. P.; HENN, R.; GREEN, J. R. & BOTTCHER, I. - Comparison of the systemic inhibitor of thromboxane synthesis anti-inflammatory activity and gastro-intestinal toxicity of non-steroidal anti-inflammatory drugs in the rat. Agents Act, 19: 374-375, 1986.
CESERANI, R.; CASCIARRI, I.; CAVALLETTI, E. & CAZZULANI, P. - Action of Nimesulide on rat gastric prostaglandins and renal function. Drug Invest, 3: 14-21, 1991.
CHENOWETH, D. E. & HUGLI, T. E. - Demonstration of specific C5a receptor on intact human polymorphonuclear leukocytes. Proc Natl Acad Sci USA, 75: 3943-3947, 1978.
CROSS, C. E.; HALLIWELL, B.; BORISH., E. T.; PRIOR, W. A.; AMES, B. N.; SAUL, R. L.; MCCORD, J. M. & HARMAN, D. - Oxigen radicals and human disease. Ann Intern Med, 107: 526-545, 1987.
CURNUTTE, J. T. & BABIOR, B. M. - Biological defense mechanism. The effect of bacteria and serum on superoxide production by granuloccytes. J Clin Invest, 53: 1662-1672, 1974.
DALLEGRI, F.; OTOONELLO, L.; GATTI, F. & GUIDI, G. - Neutrophil oxidative responses: Cell-directed and scavenging actions of anti-inflammatory drug Nimesulide. Drug Invest, 3(2): 71-74, 1991.
DE CHATELET, L. R.; SHIRLEY, P. S. & JOHNSTON, JR. R. B. - Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes. Blood, 47: 545-554, 1976.
DEL MAESTRO, R. T. - An approach to free radicals in medicine and biology. Acta Physiol Scand, 492: 153-168, 1980.
DEWALD, B.; BAGGLIOLINI, M.; CURNUTTE, J. T. & BABIOR, B. M. - Subcellular localization of the superoxide forming enzyme in human neutrophils. J Clin Invest, 63:21-29, 1979.
FANTONE, C. J. & WARD, P. A. - Role of wxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol, 107(3): 397-418, 1982.
FREEMAN, B. A. & CRAPO, J. D. - Biology of disease - Free radicals and tissue injury. Lab Invest, 17: 412-425, 1982.
GREEWALD, R. A. & MOY, W. W. - Effect of oxygendreived free radicals on hyaluronic acid. Arthritis Rheum, 23: 455-459, 1980.
LAURINDO, I. M. M.; MELLO, S. B. V. & COSSERMELLI, W. - Participação dos radicais livres de oxigênio na fisiopatologia da artrite reumatóide. Rev Hosp Clin Fac Med S Paulo, 47: 38-45, 1992.
LEGFELDER, E. - Can anti-inflammatory drugs act as scavengers of oxygen radicals? Agents Actions, 15: 56-57, 1984.
LEHRER, R. I. & COHEN, L. - Receptor-mediated regulation of superoxide production in human neutrophils stimulated by phorbol myristate acetate. J Clin Invest, 68: 1314-1320, 1981.
MAGNI, E. - Nimesulide, an overview. Drug Invest, 3: 1-3, 1991.
MELLO, S. B. V.; FARSKY, S. H. P.; SANNOMYIA, P. & GARCIA-LEME, J. - Inhibition of neutrophil chemotaxis associated with a plasma protein in aging rats: selective depression of cell responses mediated by complement-derived chemo attractants. J Leuk Biol, 51: 46-52, 1992.
MINTA, J. O. & WILLIAM, M. D. - Some nonsteroidal anti-inflammatory drugs inhibit the generation of superoxide anions by activated polymorphs by blocking ligand-receptor interactions. J Rheum, 12: 752-757, 1985.
MONBOISSE, J. C.; BRAQUET, P. & BOREL, J. P. - Oxygen-free radical as mediators of collagen breakage. Agents Actions, 15: 48-50, 1984.
MONCADA, S.; HERMAN, A. G. & VANHOUTTE, P. - Endothelium-derived relaxing factor is identified as nitrio oxide. TIPS, 8: 365-371, 1987.
SIMPSON, P. J. & LUCCHESI, B. R. - Free radicals and myocardial ischemia and reperfusion injury. J Lab Clin Med, 110: 13-25, 1987.
SWINGLE, K. F. & MOORE, G. G. I. - Pre-clinical pharmacological studies with Nimesulide. Drugs Under Exp Clin Res, 10: 587-597, 1984.
TAUBER, A. I. - Protein kinase C and the activation of the human neutrophil NADPH-oxidase. Blood, 69: 711-720, 1987.
VAN GELDER, B. F. & SLATER, E. C. - The extinction coefficient of cytochrome. Bloch Biophis Acta, 58: 593-595, 1962.
WEENING, R. S.; WEVER, R. & ROOS, D. - Quantitative aspects of the production of superoxide radicals by phagocytising human granulocytes. J Lab Clin Med, 85: 245-252, 1975.
WEISS, S. J. & WARD, P. A. - Immune complex induced generations of oxygen metabolites by human neutrophil. J Immunol, 129: 309-313, 1982.
WILLIAMS, L. T.; SNYDERMAN, R.; PIKE, M. C. & LEKOWITZ, R. L. - Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes. Proc Nat Acad Sol USA, 74: 1204-1208, 1977.
ZIGMOND, S. H. & HIRSH. J. G. - Leukocyte locomotion and chemotaxis: new method for evaluation and demonstration of cell-derived chemotactic factor. J Exp Med, 137: 387-410, 1973.
WILHELMS, O. H.; LINSSEN, M. J.; LIPPONER, L. & SEILNACHT, W. - Nimesulide, indomethacin. BW 755 C, phenidon, mepacrin and nedocromil inhibit the activation of human and rat leukocytes. Int J Tiss Reac, XII: 101-106, 1990.