The Role of Reactive Intermediates in Sulfhydryl-Dependent Immunotoxicity: Interference with Microtubule Assembly and Microtubule-dependent Cell Function

  • Richard D. Irons
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)


The critical role of protein and low molecular weight thiols in cell homeostasis has long been appreciated. Sulfhydryl(SH) reagents have been shown to interfere with numerous biochemical processes critical for cell integrity including numerous SH-dependent enzymes, protein, RNA and DNA synthesis and in the maintenance of normal intracellular redox potential. On a different level, the lymphocyte appears to be unusually sensitive to certain SH-reagents at concentrations that do not result in non-specific cytotoxicity or cell death. SH reagents, for example, are potent suppressors of normal immune cell function via mechanisms that apparently are distinct from cytotoxic events frequently associated with the exposure to SH-reactive intermediates. Both surface and intracellular SH groups have been shown to be involved in lymphocyte activation and maintenance of normal cell function, however, this discussion will be restricted largely to membrane penetrating SH-reagents.


Microtubule Assembly Sulfhydryl Reagent Lymphocyte Blastogenesis Blastogenic Response Quinone Metabolite 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aune, T. M., Webb, D. R. and Pierce, C. W., 1983, Purification and initial characterization of the lymphokine soluble immune response suppressor, J. Immunol., 131: 2848.PubMedGoogle Scholar
  2. Aune, T. M., and Pierce, C. W., 1981a, Mechanism of action of macrophage-derived suppressor factor produced by soluble immune response suppressor-treated macrophages, J. Immunol., 127: 368.PubMedGoogle Scholar
  3. Aune, T. M., and Pierce, C. W., 1981b, Identification and and initial characterization of a nonspecific suppressor factor produced by soluble immune response-treated macrophages, J. Immunol., 127: 1828.PubMedGoogle Scholar
  4. Berlin, R. D., and Ukena, T. E., 1972, Effect of colchicine and vinblastine on the agglutination of polymorphonuclear leukocytes by concanavalin A, Nature New Biol., 238: 120.PubMedCrossRefGoogle Scholar
  5. Bourguignon, L. Y. W., and Singer, S. K., 1977, Transmembrane interactions and the mechanism of capping of surface receptors by their specific ligands, Proc. Natl. Acad. Sci. USA, 74: 5031.PubMedCrossRefGoogle Scholar
  6. Chakavarty, N., and Echetebu, Z., 1978, Plasma membrane adenosine triphosphatases in rat peritoneal mast cells and macrophages-the relation of the mast cell enzyme to histamine release, Biochem. Pharmacol., 27: 1561.CrossRefGoogle Scholar
  7. Chaplin, D. D., and Wedner, H. J., 1978, Inhibition of lectin-induced lymphocyte activation by diamide and other sulfhydryl reagents, Cell. Immunol., 36: 303.PubMedCrossRefGoogle Scholar
  8. Edelman, G. M., 1973, Surface alterations and mitogenesis in lymphocytes, in: “Control of Proliferation in Animal Cells,” Cold Spring Harbor Laboratories, NY.Google Scholar
  9. Greene, W. C., Parker, C. M., and Parker, C. W., 1976, Colchicine sensitive structures and lymphocyte activation, J. Immunol., 117: 1015.PubMedGoogle Scholar
  10. Gunther, G. R., Wang, J. L. and Edelman, G. M., 1976, Kinetics of col-chicine inhibition of mitogenesis in individual lymphocytes, Exptl. Cell Res., 98: 15.PubMedCrossRefGoogle Scholar
  11. Irons, R. D. and Neptun, D. A., 1980, Effects of the principal hydroxy-metabolites of benzene on microtubule polymerization, Arch. Toxicol., 45: 297.PubMedCrossRefGoogle Scholar
  12. Irons, R. D., Neptun, D. A., and Pfeifer, R. W., 1981, Inhibition of lym- phocyte transformation and microtubule assembly by quinone metabolites of benzene: Evidence for a common mechanism, J. Reticuloendothelal Soc., 30: 359.Google Scholar
  13. Irons, R. D., Pfeifer, R. W., Aune, T. M. and Pierce, C. W., 1984, Soluble immune response suppressor ( SIRS) inhibits microtubule function in vivo and microtubule assembly in vitro, J. Immunol., 133: 2032.PubMedGoogle Scholar
  14. Jagus, R. and Kay, J. E., 1979, Distribution of lymphocyte RNA during stimulation by PHA, Eur. J. Biochem., 100: 503.PubMedCrossRefGoogle Scholar
  15. Kay, J. E., 1980, Protein synthesis during activation of lymphocytes by mitogens, Biochem. Soc. Transact., 288.Google Scholar
  16. Lagunoff, D., and Wan, H., 1979, Inhibition of histamine release from rat mast cells by cytochalasin A and other sulfhydryl reagents, Biochem. Pharmacol., 28: 1765.PubMedCrossRefGoogle Scholar
  17. Loor, F., 1977, Structure and dynamics of the lymphocyte surface in relation to differentiation, recognition and activation, Prog. Allergy, 23: 1.PubMedGoogle Scholar
  18. Mazur, M. T. and Williamson, J. R., 1977, Macrophage deformability and phagocytosis, J. Cell Biol, 75: 185.PubMedCrossRefGoogle Scholar
  19. McClain, D. A., and Edelman, G. M., 1980, Density dependent stimulation and inhibition of cell growth by agents that disrupt micro-tubules, Proc. Natl. Acad. Sci. USA, 77: 2748.PubMedCrossRefGoogle Scholar
  20. Milner, J., 1978, Is protein synthesis necessary for the commitment of lymphocytes to transformation?, Nature, 272: 628.PubMedCrossRefGoogle Scholar
  21. Nowell, P. C., 1960, Phytohemagglutinin: An initiator of mitosis in cultures of normal human leukocytes, Cancer Res., 20: 462.PubMedGoogle Scholar
  22. Pfeifer, R. W. and Irons, R. D., 1981, Inhibition of lectin-stimulated lymphocyte agglutination and mitogenesis by hydroquinone: Reactivity with intracellular sulfhydryl groups, Exptl. Mol. Pathol., 35: 189.CrossRefGoogle Scholar
  23. Pfeifer, R. W., and Irons, R. D., 1982, Effect of benzene metabolites on phytohemagglutinin-stimulated lymphopoiesis in rat bone marrow, J. Reticuloendothelial Soc., 31: 155.Google Scholar
  24. Pfeifer, R. W., and Irons, R. D., 1983, Alteration of lymphocyte function by quinones through sulfhydryl-dependent disruption of micro-tubule assembly, Intl. J. Immunopharmacol., 5: 463.CrossRefGoogle Scholar
  25. Wang, J. L., Gunther, G. R. and Edelman, G. M., 1975, Inhibition by colchicine of the mitogenic stimulation of lymphocytes prior to S phase, J. Cell Biol., 66: 128.PubMedCrossRefGoogle Scholar
  26. Watanabe, K. and West, W.L., 1982, Calmodulin, activated nucleotide phosphodiesterase, microtubules and vinca alkaloids, Fed. Proc., 41: 2292.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Richard D. Irons
    • 1
  1. 1.Chemical Industry Institute of ToxicologyResearch Triangle ParkUSA

Personalised recommendations