Skip to main content
SpringerLink
Log in

Effects of mancozeb on the activities of murine peritoneal macrophagesin vitro andex vivo

  • Article
  • Drug development
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

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-α (TNF-α) synthesis. Macrophages were examinedex 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-α) or 3 days (NO) in the presence of LPS plus IFN-γ. Macrophages from naive mice were also cultured with various concentrations of MCZ (0.05, 0.25, 0.5, 1 and 2 μg/mlL) in the presence of LPS plus IFN-γ for 2 (TNF-α) or 3 days (NO)in vitro. NO production was decreased with thein 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-α secretion with significant reduction at 2 μg/ mL MCZ. Conversely, TNF-α 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-α synthesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Binder, C., Schulz, M., Hiddemann, W., and Oellerich, M., Induction of inducible nitric oxide synthase is an essential part of tumor necrosis factor-α-induced apoptosis in MCF-7 and other epithelial tumor cells.Lab Invest., 79, 1703–1712 (1999).

    PubMed  CAS  Google Scholar 

  • Bisson, M. and Hontela, A., Cytotoxic and endocrine-disrupting potential of atrazine, diazinon, endosulfan, and mancozeb in adrenocortical steroidogenic cells of rainbow Trout exposedin vitro.Toxicol. Appl. Pharmacol., 180, 110–117 (2002).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Estlander, T., Jolanki, R., Henriks-Eckerman, M., and Kanetva, L., Occupational contact allergy to bisphenol A.Contact Dermititis, 40, 52–53 (1999).

    Article  CAS  Google Scholar 

  • 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).

    Google Scholar 

  • 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).

    Google Scholar 

  • 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).

    Article  Google Scholar 

  • Gulshan, S., Mccrrden, A. B., and Stimson, W. H., Oestrogen receptors in macrophages. Scand.J. Immunol., 31, 691–697 (1990).

    CAS  Google Scholar 

  • Hakoda, S., Ishikura, H., Takeyama, N., and Tanaka, T., Tumor necrosis factor-α-plus actinomycin D-induced apoptosis of L929 cells is prevented by nitric oxide.Surg Today, 29, 1059–1067 (1999).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Kolb, H. and Kolb-Bachofen, V., Nitric oxide in autoimmune disease: Cytotoxic or regulatory mediator.Immunol. Today, 19, 556–561 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Lukic, M. L., Popeskovic, L. and, Jan, B. D., Potentiation of immune responsiveness in rats treated with DDT.Fed. Proceed, 32, 1037 (1973).

    Google Scholar 

  • MacMicking, J., Xie, Q., and Nathan, C., Nitric oxide and macrophage function.Annu. Rev. Immunol., 15, 323–350 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Matejuk, A., Adlard, K., Zamora, A., Silverman, M., Vandenbark, A. A., and Offner, H., 17β-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).

    Article  CAS  Google Scholar 

  • Mishell, B. B. and Shiigi, S. M., Selected methods in cellular immunology. W. H. Freeman and Company, p. 14, (1980).

  • Mosmann, T., Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays.J. Immunol. Methods, 65, 55–63 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Narthan, C. F., Secretory products of macrophages.J. Clin. Invest., 79, 319–326 (1987).

    Article  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Salem, M. L., Matsuzaki, G., Madkour, G. A., and Nomoto, K., Beta-estradiol-induced decrease in IL-12 and TNF-α expression suppresses macrophage function in the course of Listeria monocytogenes function in mice.Int. J. Immunopharmacol., 21, 481–497 (1999).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • Siddiqui, A., Ali, B., and Srivastava, S. P., Effect of mancozeb on hepatic glutathione S-transferase in rat.Toxicology Letters., 68, 301–305 (1993).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Thomas, P. S., Tumor necrosis factor-α: The role of this multifunctional cytokine in asthma.Immunol. Cell. Biol., 79, 132–140 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Underhill, D. M. and Ozinsky, A., Phagocytosis of microbes: Complexity in action.Annu. Rev. Immunol., 20, 825–852 (2002).

    Article  PubMed  CAS  Google Scholar 

  • USA Environmental Protection Agency (EPA), Mancozeb Pesticide Fact Sheet (1995).

  • 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-α production by human neutrophils.J. Immunol., 152, 4102–4109 (1994).

    PubMed  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Vergova, M., Jablonica, A., and Janota, S., Occupational exposure to mancozeb in employees in the production of Novozir Mn 80.PrakovLak, 40, 425–430 (1988).

    Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Xing, Z., Current understanding of macrophage type 1 cytokine responses during intracellular infections.Histol. Histopathol., 15, 199–205 (2000).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Seoul Metropolitan Government Research Institute of Public and Environment, 137-734, Seoul, Korea

    Ae-Hee Chung & Myoung-Yun Pyo

  2. College of Pharmacy, Sookmyung Women’s University, 53-12 Chungpa-dong 2 Ka, 140-742, Yongsan-ku, Seoul, Korea

    Myoung-Yun Pyo

Authors
  1. Ae-Hee Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myoung-Yun Pyo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Myoung-Yun Pyo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chung, AH., Pyo, MY. Effects of mancozeb on the activities of murine peritoneal macrophagesin vitro andex vivo . Arch Pharm Res 28, 100–105 (2005). https://doi.org/10.1007/BF02975143

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02975143

Key words

Search

Navigation