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Effects of Mancozeb on the Activities of Murine Peritoneal Macrophages In Vitro and Ex Vivo

Chung Ae-Hee    (Seoul Metropolitan Government Research Institute of Public and Environment   ); Pyo Myoung-Yun    (College of Pharmacy, Sookmyung Women's University  );
  • 초록

    Mancozeb (MCZ) is known to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine peritoneal macrophages through evaluation of MCZ-induced alteration of nitric oxide (NO) production and tumor necrosis $factor-{\alpha}(TNF-\alpha)$ synthesis. Macrophages were examined ex vivo from mice orally treated with various doses of MCZ for 5 consecutive days per week for 4 weeks (subacute exposure, 250, 1000, 1500 mg/kg/day) followed by culture for 2 $(TNF-{\alpha})$ or 3 days (NO) in the presence of LPS plus $IFN-{\gamma}$ . Macrophages from naive mice were also cultured with various concentrations of MCZ (0.05, 0.25, 0.5, 1 and 2 ${\mu}g//mIL$ in the presence of LPS plus $IFN-{\gamma}$ for 2 $(TNF-{\alpha})$ or 3 days (NO) in vitro. NO production was decreased with the in vitro exposure to all concentrations of MCZ. However, the amount of NO production by peritoneal macrophages from MCZ-subacutely exposed mice was increased in comparision with that of control group. In vitro, MCZ suppressed $(TNF-\alpha)$ secretion with significant reduction at 2 ${\mu}g/mL$ MCZ. Conversely, $(TNF-{\alpha})$ release was enhanced ex vivo. This study provides the substantial evidence on MCZ-induced alternation in macrophage activity. In order to clearly understand the contrasting effect of MCZ on peritoneal macrophage activity, it is necessary to further investigate the influence of major metabolite of MCZ (ETU) exposure on the NO production and $(TNF-{\alpha})$ synthesis.

  • 주제어

    Mancozeb .   Macrophages .   Nitric oxide .   Tumor necrosis.  

  • 참고문헌 (38)

    1. Daniel, V., Huber, W., Baue, K., Suesal, C., Conradt, C., and Opelz, G., Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocytes subpopulations, in vitro lymphocyte reponse, plasma cytokine levels, and immunoglobulin autoantibodies. Environ. Health Perspect., 109, 173-178 (2001) 
    2. MacMicking, J., Xie, Q., and Nathan, C., Nitric oxide and macrophage function. Annu. Rev. Immunol., 15, 323-350 (1997) 
    3. Thomas, P. S., Tumor necrosis factor-${\alpha}$: The role of this multifunctional cytokine in asthma. Immunol. Cell. Biol., 79, 132-140 (2001) 
    4. Woodfork, K. A., Schuller, K. C., and Huffman, L. J., Cytokine and nitric oxide release by J774A.1 macrophages is not regulated by estradiol. Life Sci., 69, 2287-2294 (2001) 
    5. Gulshan, S., Mccrrden, A. B., and Stimson, W. H., Oestrogen receptors in macrophages. Scand. J. Immunol., 31, 691-697 (1990) 
    6. Green, L. C., Wagner, D. A., Glogowski, J. S., Skipper, P. L., Wishnok, J. S., and Tannenbaum, S. R., Analysis of nitrate, nitrite and [15N] nitrite in biological fluids. Analyt. Biochem., 126, 131-138 (1992) 
    7. Salem, M. L., Matsuzaki, G., Madkour, G. A., and Nomoto, K., Beta-estradiol-induced decrease in IL-12 and TNF-${\alpha}$ expression suppresses macrophage function in the course of Listeria monocytogenes function in mice. Int. J.Immunopharmacol., 21, 481-497 (1999) 
    8. Colosio, C., Barcellini, W., Maroni, M., Alcini, D., Bersani, M., Cavallo, D., Galli, A., Meroni, P., Pastorelli, R., Rozzardi, G. P., Soleo, L., and Foa V., Immunomodulatory effects of occupational exposure to mancozeb. Arch. Environ. Health, 51, 445-451 (1996) 
    9. Chung, H-T., Pae, H-C., Choi, B-M., Billiar, T. R., and Kim, Y-M., Nitric oxide as a bioregulator of apoptosis. Biochem. Biophys. Res. Commun., 282, 1075-1079 (2001) 
    10. Hakoda, S., Ishikura, H., Takeyama, N., and Tanaka, T., Tumor necrosis factor-${\alpha}$-plus actinomycin D-induced apoptosis of L929 cells is prevented by nitric oxide. Surg Today, 29, 1059- 1067 (1999) 
    11. Narthan, C. F., Secretory products of macrophages. J. Clin. Invest., 79, 319-326 (1987) 
    12. Vermeulen, L. A., Reinecke, A. J., and Reinecke, S. A., Evaluation of the fungicide manganese-zinc ethylene bis(dithiocarbamate) (mancozeb) for sublethal and acute toxicity to Eisenia fetida(Oligochaeta). Ecotoxico. Environ. Saf., 48, 183-189 (2001) 
    13. Shepherd, D. M., Dearstyne, E. A., and Kerkvliet, N. I., The effects of TCDD on the activation of ovalbumin(OVA)-specific DO11.10 transgenic $CD4^+$ T cells in adoptively transferred mice. Toxicol. Science, 56, 340-359 (2000) 
    14. Vegeto, E., Bonincontro, C., Pollio, G., Sala, A., Viappiani, S., Nardi, F., Brusadelli, A., Viviani, B., Ciana, P., and Maggi, A., Estrogen prevents the lipopolysaccharide-induced inflammatory response in microglia. J. Neurosci., 21, 1809- 1818 (2001) 
    15. Koch, P., Occupational allergic contact pdermatitis and airborne contact dermatitis from 5 fungicides in a vineyard worker. Cross-reactions between fungicides of the dithiocarbamate group. Contact Dermatitis, 34, 324-329 (1996) 
    16. Fine, J. S., Gasiewicz, T. A., and Silverstone, A. E., Lymphocyte stem cell alteration following perinatal exposure to 2,3,7,8- tetrachlorodibenzo-p-dioxin. Mol. Pharmacol., 35, 18-25 (1988) 
    17. Gablicks, J., Askari, E. M., and Yolen, N., DDT and immunological responses. 1. Serum antibodies and anaphylactic shock in guinea-pigs. Arch. Environ. Health, 26, 305 (1973) 
    18. Matejuk, A., Adlard, K., Zamora, A., Silverman, M., Vandenbark, A. A., and Offner, H., 17${\beta}$-estradiol inhibits cytokine, chemokine, and chemokine receptor mRNA expression in the central nerveous system of female mice with experimental autoimmune encephalomyelitis. J. Neurosci., 65, 529-542 (2001) 
    19. Mishell, B. B. and Shiigi, S. M., Selected methods in cellular immunology. W. H. Freeman and Company, p.14, (1980) 
    20. Van Dervort, A. L., Yan, L., Madara, P. J., Cobb, J. P., Wesley, R. A., Corriveau, C. C., et al., Nitric oxide regulates endotoxin induced TNF-${\alpha}$ production by human neutrophils. J. Immunol., 152, 4102-4109 (1994) 
    21. Binder, C., Schulz, M., Hiddemann, W., and Oellerich, M., Induction of inducible nitric oxide synthase is an essential part of tumor necrosis factor-${\alpha}$-induced apoptosis in MCF-7 and other epithelial tumor cells. Lab Invest., 79, 1703-1712 (1999) 
    22. Mosmann, T., Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 65, 55-63 (1983) 
    23. Zhang, X., Wang, L., Zhang, H., Guo, D., Qiao, Z., and Qiao, J., Estrogen inhibits lipopolysaccharide-induced tumor necrosis factor-alpha release from murine macrophages. Methods Fund. Exp. Clin. Pharmacol., 23, 169-173 (2001) 
    24. Vergova, M., Jablonica, A., and Janota, S., Occupational exposure to mancozeb in employees in the production of Novozir Mn 80. Prakov Lak, 40, 425-430 (1988) 
    25. Bisson, M. and Hontela, A., Cytotoxic and endocrine-disrupting potential of atrazine, diazinon, endosulfan, and mancozeb in adrenocortical steroidogenic cells of rainbow Trout exposed in vitro. Toxicol. Appl. Pharmacol., 180, 110-117 (2002) 
    26. USA Environmental Protection Agency (EPA), Mancozeb Pesticide Fact Sheet (1995) 
    27. Kackar, R., Srivastava, M. K., and Raizada, R. B., Studies on rat thyroid after oral administration of mancozeb: Morphological and biochemical evaluations. J. Appl. Toxicol., 17, 369-375 (1997) 
    28. Xing, Z., Current understanding of macrophage type 1 cytokine responses during intracellular infections. Histol. Histopathol., 15, 199-205 (2000) 
    29. Colosio, C., Fustinoni, S., Birindelli, S., Bonomi, I., Paschale, G. D., Mammone, T., Tiramani, M., Vercelli, F., Visentin, S., and Maroni, M., Ethylenethiourea in urine as an indicator of exposure to mancozeb in vineyard workers. Toxicol. Lett., 134, 133-140 (2002) 
    30. Kiekens, R. C. M., Thepen, T., Ossting, A. J., Bihari, I. C., van de Winkel, J. G. J., Bruijnzeel-Koomen, C. A. F. M., and Knol, E. F., Heterogeneity within tissue-specific macrophage and dendritic cell populations during cutaneous inflammation in atopic dermatitis. Br. J. Dermatol., 145, 957-965 (2001) 
    31. Ruh, M. F., Bi, Y., Cox, D., Berk, D., Howlett, A. C., and Bellone, C. J., Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line. Endocrine, 9, 207-211 (1998) 
    32. Stefano, G. B., Prevot, V., Beauvillain, J. C., Fimiani, C., Welters, I., Cadet, P., Breton, C., Pestel, J., Salzet, M., and Bilfinger, T. V., Estradiol coupling to human monocytes nitric oxide release is dependent on intracellular calcium transients: Evidence for an estrogen surface receptor. J. Immunol., 163, 3758-5763 (1999) 
    33. Estlander, T., Jolanki, R., Henriks-Eckerman, M., and Kanerva, L., Occupational contact allergy to bisphenol A. Contact Dermititis, 40, 52-53 (1999) 
    34. Underhill, D. M. and Ozinsky, A., Phagocytosis of microbes: Complexity in action. Annu. Rev. Immunol., 20, 825-852 (2002) 
    35. Siddiqui, A., Ali, B., and Srivastava, S. P., Effect of mancozeb on hepatic glutathione S-transferase in rat. Toxicology Letters., 68, 301-305 (1993) 
    36. Kim, Y. M., Talanian, R. V., Li, J., and Billiar, T. R., Nitric oxide inhibits apoptosis by preventing increases in caspase-3-like activity via two distinct mechanisms. J. Bio. Chem., 272, 31138-31148 (1997) 
    37. Kolb, H. and Kolb-Bachofen, V., Nitric oxide in autoimmune disease: Cytotoxic or regulatory mediator. Immunol., Today, 19, 556-561 (1998) 
    38. Lukic, M. L., Popeskovic, L., and Jan, B. D., Potentiation of immune responsiveness in rats treated with DDT. Fed. Proceed., 32, 1037 (1973) 

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