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. 2003 May;111(5):708–713. doi: 10.1289/ehp.5960

Environmentally relevant metal and transition metal ions enhance Fc epsilon RI-mediated mast cell activation.

Aurelia Walczak-Drzewiecka 1, Janina Wyczólkowska 1, Jaroslaw Dastych 1
PMCID: PMC1241479  PMID: 12727598

Abstract

Upon contact with allergen, sensitized mast cells release highly active proinflammatory mediators. Allergen-mediated mast cell activation is an important mechanism in the pathogenesis of atopic asthma. Asthmatic patients are especially susceptible to air pollution. Epidemiologic studies found a positive correlation between severity of symptoms among asthmatic patients and the level of particulate matter (PM) in the air. Among the constituents of PM are metals and transition metals, which could mediate some of its adverse effects on human health. We sought to determine the effect of metal and transition metal ions on allergen-mediated mast cell activation. We observed that several metal and transition metal ions activated mast cells and enhanced allergen-mediated mast cell activation. Thus, Al(3+), Cd(2+), and Sr(2+) induced release of granule-associated N-acetyl-ss-d-hexosaminidase, and Al(3+) and Ni(2+) enhanced antigen-mediated release. Metal and transition metal ions also induced significant secretion of interleukin (IL)-4 and increased antigen-mediated IL-4 secretion in mast cells. These effects of metal and transition metal ions on mast cells were observed at concentrations that do not result in direct cytotoxicity and might be relevant for environmental exposure. Thus, metals and transition metals could increase the level of allergen-mediated mast cell activation, which might be one of the mechanisms mediating exacerbation of allergen-driven asthma symptoms by air pollution.

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Selected References

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  1. Andersen I., Svenes K. Establishing normal values for nickel in human lung disease. J Environ Monit. 1999 Dec;1(6):553–555. doi: 10.1039/a905924e. [DOI] [PubMed] [Google Scholar]
  2. Angerer J., Lehnert G. Occupational chronic exposure to metals. II. Nickel exposure of stainless steel welders--biological monitoring. Int Arch Occup Environ Health. 1990;62(1):7–10. doi: 10.1007/BF00397842. [DOI] [PubMed] [Google Scholar]
  3. Balachandran S., Meena B. R., Khillare P. S. Particle size distribution and its elemental composition in the ambient air of Delhi. Environ Int. 2000 Aug;26(1-2):49–54. doi: 10.1016/s0160-4120(00)00077-5. [DOI] [PubMed] [Google Scholar]
  4. Benhamou M., Gutkind J. S., Robbins K. C., Siraganian R. P. Tyrosine phosphorylation coupled to IgE receptor-mediated signal transduction and histamine release. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5327–5330. doi: 10.1073/pnas.87.14.5327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bigazzi P. E. Metals and kidney autoimmunity. Environ Health Perspect. 1999 Oct;107 (Suppl 5):753–765. doi: 10.1289/ehp.99107s5753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown M. A., Hural J. Functions of IL-4 and control of its expression. Crit Rev Immunol. 1997;17(1):1–32. doi: 10.1615/critrevimmunol.v17.i1.10. [DOI] [PubMed] [Google Scholar]
  7. Busse W. W., Lemanske R. F., Jr Asthma. N Engl J Med. 2001 Feb 1;344(5):350–362. doi: 10.1056/NEJM200102013440507. [DOI] [PubMed] [Google Scholar]
  8. Cirla A. M. Cobalt-related asthma: clinical and immunological aspects. Sci Total Environ. 1994 Jun 30;150(1-3):85–94. doi: 10.1016/0048-9697(94)90133-3. [DOI] [PubMed] [Google Scholar]
  9. Costa D. L., Dreher K. L. Bioavailable transition metals in particulate matter mediate cardiopulmonary injury in healthy and compromised animal models. Environ Health Perspect. 1997 Sep;105 (Suppl 5):1053–1060. doi: 10.1289/ehp.97105s51053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dastych J., Hardison M. C., Metcalfe D. D. Aggregation of low affinity IgG receptors induces mast cell adherence to fibronectin: requirement for the common FcR gamma-chain. J Immunol. 1997 Feb 15;158(4):1803–1809. [PubMed] [Google Scholar]
  11. Dastych J., Walczak-Drzewiecka A., Wyczolkowska J., Metcalfe D. D. Murine mast cells exposed to mercuric chloride release granule-associated N-acetyl-beta-D-hexosaminidase and secrete IL-4 and TNF-alpha. J Allergy Clin Immunol. 1999 Jun;103(6):1108–1114. doi: 10.1016/s0091-6749(99)70186-7. [DOI] [PubMed] [Google Scholar]
  12. Demo S. D., Masuda E., Rossi A. B., Throndset B. T., Gerard A. L., Chan E. H., Armstrong R. J., Fox B. P., Lorens J. B., Payan D. G. Quantitative measurement of mast cell degranulation using a novel flow cytometric annexin-V binding assay. Cytometry. 1999 Aug 1;36(4):340–348. doi: 10.1002/(sici)1097-0320(19990801)36:4<340::aid-cyto9>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  13. Domingo J. L. Metal-induced developmental toxicity in mammals: a review. J Toxicol Environ Health. 1994 Jun;42(2):123–141. doi: 10.1080/15287399409531868. [DOI] [PubMed] [Google Scholar]
  14. Donaldson K., Gilmour M. I., MacNee W. Asthma and PM10. Respir Res. 2000 Jul 3;1(1):12–15. doi: 10.1186/rr5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Donaldson K., MacNee W. Potential mechanisms of adverse pulmonary and cardiovascular effects of particulate air pollution (PM10). Int J Hyg Environ Health. 2001 Jul;203(5-6):411–415. doi: 10.1078/1438-4639-00059. [DOI] [PubMed] [Google Scholar]
  16. Gavett S. H., Koren H. S. The role of particulate matter in exacerbation of atopic asthma. Int Arch Allergy Immunol. 2001 Jan-Mar;124(1-3):109–112. doi: 10.1159/000053685. [DOI] [PubMed] [Google Scholar]
  17. Ghio A. J., Carter J. D., Samet J. M., Reed W., Quay J., Dailey L. A., Richards J. H., Devlin R. B. Metal-dependent expression of ferritin and lactoferrin by respiratory epithelial cells. Am J Physiol. 1998 May;274(5 Pt 1):L728–L736. doi: 10.1152/ajplung.1998.274.5.L728. [DOI] [PubMed] [Google Scholar]
  18. Gordon J. R., Burd P. R., Galli S. J. Mast cells as a source of multifunctional cytokines. Immunol Today. 1990 Dec;11(12):458–464. doi: 10.1016/0167-5699(90)90176-a. [DOI] [PubMed] [Google Scholar]
  19. Hamawy M. M., Mergenhagen S. E., Siraganian R. P. Protein tyrosine phosphorylation as a mechanism of signalling in mast cells and basophils. Cell Signal. 1995 Aug;7(6):535–544. doi: 10.1016/0898-6568(95)00024-j. [DOI] [PubMed] [Google Scholar]
  20. Hart P. H. Regulation of the inflammatory response in asthma by mast cell products. Immunol Cell Biol. 2001 Apr;79(2):149–153. doi: 10.1046/j.1440-1711.2001.00983.x. [DOI] [PubMed] [Google Scholar]
  21. Heinrich J., Hoelscher B., Wjst M., Ritz B., Cyrys J., Wichmann H. Respiratory diseases and allergies in two polluted areas in East Germany. Environ Health Perspect. 1999 Jan;107(1):53–62. doi: 10.1289/ehp.9910753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Heo Y., Lee W. T., Lawrence D. A. In vivo the environmental pollutants lead and mercury induce oligoclonal T cell responses skewed toward type-2 reactivities. Cell Immunol. 1997 Aug 1;179(2):185–195. doi: 10.1006/cimm.1997.1160. [DOI] [PubMed] [Google Scholar]
  23. Hrsak J., Sega K., Balăgović I. Lead, manganese, and cadmium content in PM10 and PM2.5 particle fractions--a pilot study. Arh Hig Rada Toksikol. 2000 Jun;51(2):243–247. [PubMed] [Google Scholar]
  24. Ikai K., Danno K., Horio T., Narumiya S. Effect of ultraviolet irradiation on mast cell-deficient W/Wv mice. J Invest Dermatol. 1985 Jul;85(1):82–84. doi: 10.1111/1523-1747.ep12275365. [DOI] [PubMed] [Google Scholar]
  25. Kanerva L., Jolanki R., Estlander T., Alanko K., Savela A. Incidence rates of occupational allergic contact dermatitis caused by metals. Am J Contact Dermat. 2000 Sep;11(3):155–160. doi: 10.1053/ajcd.2000.7186. [DOI] [PubMed] [Google Scholar]
  26. Kent U. M., Mao S. Y., Wofsy C., Goldstein B., Ross S., Metzger H. Dynamics of signal transduction after aggregation of cell-surface receptors: studies on the type I receptor for IgE. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3087–3091. doi: 10.1073/pnas.91.8.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kiely P. D., Pecht I., Oliveira D. B. Mercuric chloride-induced vasculitis in the Brown Norway rat: alpha beta T cell-dependent and -independent phases: role of the mast cell. J Immunol. 1997 Nov 15;159(10):5100–5106. [PubMed] [Google Scholar]
  28. Kleeberger S. R., Ohtsuka Y., Zhang L. Y., Longphre M. Airway responses to chronic ozone exposure are partially mediated through mast cells. J Appl Physiol (1985) 2001 Feb;90(2):713–723. doi: 10.1152/jappl.2001.90.2.713. [DOI] [PubMed] [Google Scholar]
  29. Klein C. L., Köhler H., Kirkpatrick C. J. Increased adhesion and activation of polymorphonuclear neutrophil granulocytes to endothelial cells under heavy metal exposure in vitro. Pathobiology. 1994;62(2):90–98. doi: 10.1159/000163883. [DOI] [PubMed] [Google Scholar]
  30. Lambert A. L., Dong W., Selgrade M. K., Gilmour M. I. Enhanced allergic sensitization by residual oil fly ash particles is mediated by soluble metal constituents. Toxicol Appl Pharmacol. 2000 May 15;165(1):84–93. doi: 10.1006/taap.2000.8932. [DOI] [PubMed] [Google Scholar]
  31. Lutz P. M., Wilson T. J., Ireland J., Jones A. L., Gorman J. S., Gale N. L., Johnson J. C., Hewett J. E. Elevated immunoglobulin E (IgE) levels in children with exposure to environmental lead. Toxicology. 1999 May 3;134(1):63–78. doi: 10.1016/s0300-483x(99)00036-0. [DOI] [PubMed] [Google Scholar]
  32. Maddox Lee, Schwartz David A. The pathophysiology of asthma. Annu Rev Med. 2002;53:477–498. doi: 10.1146/annurev.med.53.082901.103921. [DOI] [PubMed] [Google Scholar]
  33. McCabe M. J., Jr, Lawrence D. A. The heavy metal lead exhibits B cell-stimulatory factor activity by enhancing B cell Ia expression and differentiation. J Immunol. 1990 Jul 15;145(2):671–677. [PubMed] [Google Scholar]
  34. Metcalfe D. D., Baram D., Mekori Y. A. Mast cells. Physiol Rev. 1997 Oct;77(4):1033–1079. doi: 10.1152/physrev.1997.77.4.1033. [DOI] [PubMed] [Google Scholar]
  35. Murdoch R. D., Pepys J., Hughes E. G. IgE antibody responses to platinum group metals: a large scale refinery survey. Br J Ind Med. 1986 Jan;43(1):37–43. doi: 10.1136/oem.43.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nixon D. E., Moyer T. P., Squillace D. P., McCarthy J. T. Determination of serum nickel by graphite furnace atomic absorption spectrometry with Zeeman-effect background correction: values in a normal population and a population undergoing dialysis. Analyst. 1989 Dec;114(12):1671–1674. doi: 10.1039/an9891401671. [DOI] [PubMed] [Google Scholar]
  37. Norseth T. Metal carcinogenesis. Ann N Y Acad Sci. 1988;534:377–386. doi: 10.1111/j.1749-6632.1988.tb30125.x. [DOI] [PubMed] [Google Scholar]
  38. Ormstad H. Suspended particulate matter in indoor air: adjuvants and allergen carriers. Toxicology. 2000 Nov 2;152(1-3):53–68. doi: 10.1016/s0300-483x(00)00292-4. [DOI] [PubMed] [Google Scholar]
  39. Ozkaynak H., Xue J., Spengler J., Wallace L., Pellizzari E., Jenkins P. Personal exposure to airborne particles and metals: results from the Particle TEAM study in Riverside, California. J Expo Anal Environ Epidemiol. 1996 Jan-Mar;6(1):57–78. [PubMed] [Google Scholar]
  40. Probst P., Küntzlin D., Fleischer B. TH2-type infiltrating T cells in nickel-induced contact dermatitis. Cell Immunol. 1995 Oct 1;165(1):134–140. doi: 10.1006/cimm.1995.1196. [DOI] [PubMed] [Google Scholar]
  41. Prouvost-Danon A., Abadie A., Sapin C., Bazin H., Druet P. Induction of IgE synthesis and potentiation of anti-ovalbumin IgE antibody response by HgCl2 in the rat. J Immunol. 1981 Feb;126(2):699–792. [PubMed] [Google Scholar]
  42. Razin E., Mencia-Huerta J. M., Stevens R. L., Lewis R. A., Liu F. T., Corey E., Austen K. F. IgE-mediated release of leukotriene C4, chondroitin sulfate E proteoglycan, beta-hexosaminidase, and histamine from cultured bone marrow-derived mouse mast cells. J Exp Med. 1983 Jan 1;157(1):189–201. doi: 10.1084/jem.157.1.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Revoltella R., Ovary Z. Preferential production of rabbit reaginic antibodies. Int Arch Allergy Appl Immunol. 1969;36(3):282–289. doi: 10.1159/000230749. [DOI] [PubMed] [Google Scholar]
  44. Rondeau V., Commenges D., Jacqmin-Gadda H., Dartigues J. F. Relation between aluminum concentrations in drinking water and Alzheimer's disease: an 8-year follow-up study. Am J Epidemiol. 2000 Jul 1;152(1):59–66. doi: 10.1093/aje/152.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Samet J. M., Stonehuerner J., Reed W., Devlin R. B., Dailey L. A., Kennedy T. P., Bromberg P. A., Ghio A. J. Disruption of protein tyrosine phosphate homeostasis in bronchial epithelial cells exposed to oil fly ash. Am J Physiol. 1997 Mar;272(3 Pt 1):L426–L432. doi: 10.1152/ajplung.1997.272.3.L426. [DOI] [PubMed] [Google Scholar]
  46. Schwartz L. B., Austen K. F. Enzymes of the mast cell granule. J Invest Dermatol. 1980 May;74(5):349–353. doi: 10.1111/1523-1747.ep12543620. [DOI] [PubMed] [Google Scholar]
  47. Schwartz L. B., Austen K. F., Wasserman S. I. Immunologic release of beta-hexosaminidase and beta-glucuronidase from purified rat serosal mast cells. J Immunol. 1979 Oct;123(4):1445–1450. [PubMed] [Google Scholar]
  48. Schwartz L. B., Lewis R. A., Seldin D., Austen K. F. Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells. J Immunol. 1981 Apr;126(4):1290–1294. [PubMed] [Google Scholar]
  49. Smith-Sivertsen T., Lund E., Thomassen Y., Norseth T. Human nickel exposure in an area polluted by nickel refining: the Sør-Varanger study. Arch Environ Health. 1997 Nov-Dec;52(6):464–471. doi: 10.1080/00039899709602225. [DOI] [PubMed] [Google Scholar]
  50. Stejskal Jenny, Stejskal Vera DM. The role of metals in autoimmunity and the link to neuroendocrinology. Neuro Endocrinol Lett. 1999;20(6):351–364. [PubMed] [Google Scholar]
  51. Suzuki Y., Yoshimaru T., Yamashita K., Matsui T., Yamaki M., Shimizu K. Exposure of RBL-2H3 mast cells to Ag(+) induces cell degranulation and mediator release. Biochem Biophys Res Commun. 2001 May 11;283(3):707–714. doi: 10.1006/bbrc.2001.4844. [DOI] [PubMed] [Google Scholar]
  52. Szepietowski J. C., McKenzie R. C., Keohane S. G., Aldridge R. D., Hunter J. A. Atopic and non-atopic individuals react to nickel challenge in a similar way. A study of the cytokine profile in nickel-induced contact dermatitis. Br J Dermatol. 1997 Aug;137(2):195–200. doi: 10.1046/j.1365-2133.1997.18051888.x. [DOI] [PubMed] [Google Scholar]
  53. Taylor M. L., Metcalfe D. D. Mast cells in allergy and host defense. Allergy Asthma Proc. 2001 May-Jun;22(3):115–119. doi: 10.2500/108854101778148764. [DOI] [PubMed] [Google Scholar]
  54. Williams C. M., Galli S. J. The diverse potential effector and immunoregulatory roles of mast cells in allergic disease. J Allergy Clin Immunol. 2000 May;105(5):847–859. doi: 10.1067/mai.2000.106485. [DOI] [PubMed] [Google Scholar]

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