Skip to main content
SpringerLink
Log in

Study of Response of Thymic and Submaxillary Lymph Node Lymphocytes to Administration of Lead by Different Routes

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

A number of studies have reported that heavy metals are not only toxic for the organism but they may modulate immune responses. In the current study, the effect of 4-week administration of 200 ppm of PbAc2, using different routes of administration (orally and intraperitoneal injection), on lymphatic organs was evaluated. In the thymus, the number of lymphocyte cells and the cellularity diminished significantly for both routes of treatment. Regarding the submaxillary lymph nodes, no significant variations took place. Cell-mediated immune response is commonly evaluated by cell proliferation assays. Mitogens are known to induce a vigorous proliferative response in lymphoid cells from mammals. An increase in the proliferation of T lymphocytes stimulated by concanavalin A and the proliferation of B lymphocytes stimulated with lipopolysaccharides was found in thymus for both routes of administration, whereas in the lymph nodes, there was a decrease in proliferation of T lymphocytes. Furthermore, lead administration by intraperitoneal route caused an effect on B and T lymphocyte subpopulations. Thus, there was an increase in B+ cells and a decrease in T+ cells. Regarding CD4+ and CD8+ T cells, there were only variations, concretely a drop in both subpopulations, in lymph nodes when lead was administered intraperitoneally. It is important to emphasize that an increase in apoptosis was found in this tissue. At the histological level, evident alterations were described in thymus both for the oral and for the intraperitoneal route. Therefore, it is possible to show that lead administered by both routes generated effects on an immunological level.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Patrick L (2006) Lead toxicity, a review of the literature. Part I: exposure, evaluation, and treatment. Altern Med Rev 11:2–22

    PubMed  Google Scholar 

  2. Verstraeten SV, Aimo L, Oteiza PI (2008) Aluminium and lead: molecular mechanisms of brain toxicity. Arch Toxicol 82:789–802

    Article  CAS  PubMed  Google Scholar 

  3. Dietert RR, Piepenbrink MS (2006) Lead and immune function. Crit Rev Toxicol 36:359–385

    Article  CAS  PubMed  Google Scholar 

  4. Farrer DG, Hueber S, Laiosa MD, Eckles KG, McCabe MJ Jr (2008) Reduction of myeloid suppressor cell derived nitric oxide provides a mechanistic basis of lead enhancement of alloreactive CD4+T cell proliferation. Toxicol Appl Pharmacol 229:135–145

    Article  CAS  PubMed  Google Scholar 

  5. McCabe MJ Jr, Singh KP, Reiners JJ Jr (2001) Low level lead exposure in vitro stimulates the proliferation and expansion of alloantigen-reactive CD4 (high) T cells. Toxicol Appl Pharmacol 177:219–231

    Article  CAS  PubMed  Google Scholar 

  6. McCabe MJ Jr, Singh KP, Reiners JJ Jr (1999) Lead intoxication impairs the generation of a delayed type hypersensitivity response. Toxicology 139:255–264

    Article  CAS  PubMed  Google Scholar 

  7. Bernier J, Brousseau P, Krzystyniak K, Tryphonas H, Fournier M (1995) Immunotoxicity of heavy metals in relation to Great Lakes. Environ Health Perspect 103:23–34

    Article  CAS  PubMed  Google Scholar 

  8. Colombo M, Hamelin C, Kouassi E, Fournier M, Bernier J (2004) Differential effects of mercury, lead, and cadmium on IL-2 production by Jurkat T cells. Clin Immunol 111:311–322

    Article  CAS  PubMed  Google Scholar 

  9. Razani-Boroujerdi S, Edwards B, Sopori ML (1999) Lead stimulates lymphocyte proliferation through enhanced T cell-B cell interaction. J Pharmacol Exp Ther 288:714–719

    CAS  PubMed  Google Scholar 

  10. Tsuruoka S, Sugimoto K, Muto S, Nomiyama K, Fujimura A, Imai M (2000) Acute effect of cadmium-metallothionein on glucose and aminoacid transport across the apical membrane of the rabbit proximal tubule perfused in vitro. J Pharmacol Exp Ther 292:769–777

    CAS  PubMed  Google Scholar 

  11. Oberto A, Marks N, Evans HL, Guidotti A (1996) Lead promotes apoptosis in newborn rat cerebellar neurons: pathological implications. J Pharmacol Exp Ther 279:435–442

    CAS  PubMed  Google Scholar 

  12. Tavakoli-Nezhad M, Barron AJ, Pitts DK (2001) Postnatal inorganic lead exposure decreases the number of spontaneously active midbrain dopamine neurons in the rat. Neurotoxicology 22:259–269

    Article  CAS  PubMed  Google Scholar 

  13. Zhang J, Wang XF, Lu ZB, Liu NQ, Zhao BL (2004) The effects of meso-2, 3-dimercaptosuccinic acid and oligomeric procyanidins on acute lead neurotoxicity in rat hippocampus. Free Radic Biol Med 37:1037–1050

    Article  CAS  PubMed  Google Scholar 

  14. Capri M, Quaglino D, Verzella D, Monti D, Bonafè M, Cossarizza A, Troiano L, Zecca L, Pasquali-Ronchetti I, Franceschi C (2000) A cytofluorometric study of T lymphocyte subsets in rat lymphoid tissues (thymus, lymph nodes) and peripheral blood: a continuous remodelling during the first year of life. Exp Gerontol 35:613–625

    Article  CAS  PubMed  Google Scholar 

  15. Živković IP, Rakin AK, Petrović-Djergović DM, Kosec DJ, Mićić MV (2005) Exposure to forced swim stress alters morphofunctional characteristics of the rat thymus. J Neuroimmunol 160:77–86

    Article  PubMed  Google Scholar 

  16. Kelly K, Pilarski L, Shortman K, Scollay R (1988) CD4+CD8+ cells are rare among in vitro activated mouse or human T lymphocytes. Cell Immunol 117:414–424

    Article  CAS  PubMed  Google Scholar 

  17. Hillemeyer P, White MD, Pascual DW (2002) Development of a transient CD4+CD8+ T cell subset in the cervical lymph nodes following intratracheal instillation with an adenovirus vector. Cell Immunol 215:173–185

    Article  CAS  PubMed  Google Scholar 

  18. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314

    Article  CAS  PubMed  Google Scholar 

  19. Olmo N, Turnay J, González de Buitrago G, López de Silanes I, Gavilanes JG, Lizarbe MA (2001) Cytotoxic mechanism of the ribotoxin alpha-sarcin. Induction of cell death via apoptosis. Eur J Biochem 268:2113–2123

    Article  CAS  PubMed  Google Scholar 

  20. Coscia GC, Discalzi G, Ponzetti C (1987) Immunological aspects of occupational lead exposure. Med Lav 78:360–364

    CAS  PubMed  Google Scholar 

  21. Fischbein A, Tsang P, Luo JC, Bekesi JG (1993) The immune system as target for subclinical lead related toxicity. Br J Ind Med 50:185–186

    CAS  PubMed  Google Scholar 

  22. Farrer DG, Hueber SM Jr, Mc Cabe MJ (2005) Lead enhances CD4+ T cell proliferation indirectly by targeting antigen presenting cells and modulating antigen-specific interactions. Toxicol Appl Pharmacol 207:125–137

    Article  CAS  PubMed  Google Scholar 

  23. Teijón C, Olmo R, Blanco MD, Romero A, Teijón JM (2003) Effects of lead administration at low doses by different routes on rat spleens. Study of response of splenic lymphocytes and tissue lysozyme. Toxicology 191:245–258

    Article  PubMed  Google Scholar 

  24. Krocova Z, Macela A, Kroca M, Hernychova L (2000) The immunomodulatory effect(s) of lead and cadmium on the cells of immune system in vitro. Toxicol In Vitro 14:33–40

    Article  CAS  PubMed  Google Scholar 

  25. Teijón C, del Socorro JM, Martín JA, Lozano M, Bernardo MV, Blanco MD (2000) Lead accumulation in rats at nonacute doses and short periods of time: hepatic, renal and hematological effects. Ecotoxicol Environ Restoration 3:36–41

    Google Scholar 

  26. Engler H, Stefanski V (2003) Social stress and T cell maturation in male rats: transient and persistent alterations in thymic function. Psychoneuroendocrinology 28:951–969

    Article  PubMed  Google Scholar 

  27. Kim YO, Pyo MY, Kim JH (2000) Influence of melatonin on immunotoxicity of lead. Int J Immunopharmacol 22:821–832

    Article  CAS  PubMed  Google Scholar 

  28. Kamath AB, Xu H, Nagarkatti PS, Nagarkatti M (1997) Evidence for the induction of apoptosis in thymocytes by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in vivo. Toxicol Appl Pharmacol 142:367–377

    Article  CAS  PubMed  Google Scholar 

  29. Luster MI, Blank JA (1987) Molecular and cellular basis of chemically induced immunotoxicity. Annu Rev Pharmacol Toxicol 27:23–31

    Article  CAS  PubMed  Google Scholar 

  30. Fischbein A, Tsang P, Luo JJ, Roboz JP, Jiang JG, Bekesi JG (1993) Phenotypic abberations of CD3+ and CD4+ cells and functional impairments of lymphocytes at low-level occupational exposure to lead. Clin Immunol Immunopathol 66:163–168

    Article  CAS  PubMed  Google Scholar 

  31. Felten DL, Overhage JM, Felten SY, Schmedtje JF (1981) Noradrenergic sympathetic innervation of lymphoid tissue in the rabbit appendix: further evidence for a link between the nervous and immune systems. Brain Res Bull 7:595–612

    Article  CAS  PubMed  Google Scholar 

  32. Leposavić G, Plećaš B, Kosec D (2000) Differential effects of chronic propanolol treatment on the phenotypic profile of thymocytes from immature and adult rats. Immunopharmacology 46:79–87

    Article  PubMed  Google Scholar 

  33. Quaglino D, Ronchetti P (2001) Cell death in the rat thymus: a minireview. Apoptosis 6:398–401

    Article  Google Scholar 

  34. Kaioumova D, Kaioumov F, Opelz G, Süsal C (2001) Toxic effects of the herbicide 2, 4-dichlorophenoxyacetic acid on lymphoid organs of the rat. Chemosphere 43:801–805

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by a grant (07N/0102/2002) from the Comunidad Autónoma de Madrid (Spain).

Author information

Authors and Affiliations

  1. Escuela Universitaria de Enfermería, Fisioterapia y Podología, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, 28040, Spain

    César Teijón, Juan Vicente Beneit & Antonio Luis Villarino

  2. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, 28040, Spain

    María Dolores Blanco, Carlos Santiago Romero, Sandra Guerrero & Rosa Olmo

Authors
  1. César Teijón
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. María Dolores Blanco
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlos Santiago Romero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juan Vicente Beneit
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Luis Villarino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sandra Guerrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rosa Olmo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to María Dolores Blanco.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Teijón, C., Blanco, M.D., Romero, C.S. et al. Study of Response of Thymic and Submaxillary Lymph Node Lymphocytes to Administration of Lead by Different Routes. Biol Trace Elem Res 135, 74–85 (2010). https://doi.org/10.1007/s12011-009-8495-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-009-8495-6

Keywords

Search

Navigation