Skip to main content
SpringerLink
Log in

Cellular and mediator profile in bronchoalveolar lavage of guinea pigs after toluene diisocyanate (TDI) exposure

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Toluene diisocyanate (TDI) is a volatile, highly reactive chemical widely used as a polymerizing agent in the production of polyurethane foams, lacquers, adhesives, and other items. Repeated airway exposures in the workplace to TDI may cause a concentration-dependent risk of developing chronic airway disorders. Different pathomechanisms are involved. IgE-mediated sensitization and irritative effects were clearly demonstrated in exposed subjects as well as in animals. In this study we examined the cellular and mediator composition in bronchoalveolar lavage fluid (BALF) of guinea pigs (eight in each group) exposed to TDI (10, 20, or 30 ppb) on 5 consecutive days for 2 hours each. Increased numbers of eosinophils and significantly elevated levels of LTB4 and LTC4/LTD4/LTE4 were obtained in BALF of all exposed animals when compared to nonexposed control animals. PGD2 and TXB2 remained unaltered in BALF. Stimulation of BALF cells of exposed and control animals with Ca-ionophore A23187 and arachidonic acid induced an increased generation of LTB4. Furthermore, BALF cells of the exposed animal groups generated immunoreactive LTC4/LTD4/LTE4, whereas controls did not show peptido-leukotriene formation in the presence and absence of stimuli. Our data clearly demonstrate an influx of eosinophils into the airways associated with mediator release and higher cellular responsiveness after TDI exposure.

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

  1. Baur X (1990) New aspects of isocyanate asthma. Lung (Suppl) 606–613

  2. Bentley AM, Maestrelli P, Saetta M, Fabbri LM, Robinson DS, Bradley BL, Jeffery PK, Durham SR, Kay AB (1992) Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma. J Allergy Clin Immunol 89:821–829

    Google Scholar 

  3. Bradford MM(1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye-binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  4. Coleridge HM, Coleridge JCG, Ginzel KH, Baker DG, Banzett RB, Morrison MA (1976) Stimulation of “irritant” receptors and afferent C-fibers in the lungs by prostaglandins. Nature 264:451–453

    Google Scholar 

  5. Dahlén S, Hansson G, Hedqvist P, Bjorck T, Granstrom E (1983) Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4. Proc Natl Acad Sci USA 80:1712–1716

    Google Scholar 

  6. Erjefält I, Perrson CGA (1992) Increased sensitivity to toluene diisocyanate (TDI) in airways previously exposed to low doses of TDI. Clin Exp Allergy 22:854–862

    Google Scholar 

  7. Fabbri ML, Boschetto P, Zocca E, Milani G, Pivirotto F, Plebani M, Burlina A, Licata B, Mapp CE (1987) Bronchoalveolar neutrophilia during late asthmatic reactions induced by toluene diisocyanate. Am Rev Respir Dis 136:36–42

    Google Scholar 

  8. Ford-Hutchinson AW, Bray MA, Doig MV, Shipley ME, Smith MJ (1980) Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286:264–265

    Google Scholar 

  9. Goetzl EJ, Pickett WC (1980) The human PMN leukocyte chemotactic activity of complex hydroxyeicosatetraenoic acids (HETEs). J Immunol 125:1789–1791

    Google Scholar 

  10. Gordon T, Sheppard D, McDonald DM, Distefano S, Scypinski L (1985) Airway hyperresponsiveness and inflammation induced by toluene diisocyanate in guinea pigs. Am Rev Respir Dis 132:1106–1112

    Google Scholar 

  11. Hamel R, Ford-Hutchinson AW (1983) Bronchoconstrictor effects of leukotriene B4 in the guinea pig in vivo. Prostaglandins 25:405–412

    Google Scholar 

  12. Hesbert A, Ban M, Bonnet P, Simon P, Bottin MC, Lemonnier M, de Ceaurriz J (1991) Interdependence of polymorphonuclear neutrophils and macrophages stained for N-acetyl-β-glucosaminidase in lavage effluents from toluene diisocyanate-exposed rat lungs. Toxicol Lett 56:53–59

    Google Scholar 

  13. Holtzman MJ (1991) Arachidonic acid metabolism; implications of biological chemistry for lung function and disease. Am Rev Respir Dis 143:188–203

    Google Scholar 

  14. Ingenito EP, Pliss LB, Ingram RH, Pichurko BM (1990) Bronchoalveolar lavage cell and mediator responses to hyperpnea-induced bronchoconstriction in the guinea pig. Am Rev Respir Dis 141:1162–1166

    Google Scholar 

  15. Karaouglu K, Marek W, Potthast J, Marczynski B, Baur X (1992) Alteration of bronchial smooth muscle responses to acetylcholine by isocyanates in guinea pig trachea. Eur Respir J 5/15:271

    Google Scholar 

  16. Karol MH, Alarie YC (1978) Tolyl-specific IgE antibodies in workers with hypersensitivity to toluene diisocyanate. Am Ind Hyg Assoc J 39:454–458

    Google Scholar 

  17. Karol MH (1983) Concentration-dependent immunologic response to toluene diisocyanate (TDI) following inhalation exposure. Toxicol Appl Pharmacol 68:229–241

    Google Scholar 

  18. Kay AB (1991) Asthma and inflammation. J Allergy Clin Immunol 87:893–910

    Google Scholar 

  19. Mapp CE, Giacomo GR, Omini C, Broseghini C, Fabbri LM (1986) Late but not early, asthmatic reactions induced by toluene-diisocyanate are associated with increased airway responsiveness to methacholine. Eur J Respir Dis 69:276–284

    Google Scholar 

  20. Marczynski B, Czuppon AB, Marek W, Baur X (1992) Indication of DNA strand breaks in human white blood cells after in vitro exposure to toluene diisocyanate (TDI). Toxicol Ind Health 8:157–169

    Google Scholar 

  21. Marek W, Potthast J, Marczynski B, Baur X (1993) Alteration of smooth muscles responses acetylcholine induced by toluene diisocyanate (TDI) and neuropeptides in guinea pigs. Chiers voor Arbeitsgeneesekunde-Cahiers de Medecine du Travail vol. XXXL No 1–1994:45–47

    Google Scholar 

  22. Raulf M, König W (1991) Modulation of leukotriene release from human polymorphonuclear granulocytes by polychlorinated biphenyls (PCB). Immunology 73:485–490

    Google Scholar 

  23. Vandenplas O, Malo JL, Saetta M, Mapp CE, Fabbri LM (1993) Occupational asthma and extrinsic alveolitis due to isocyanates. Current status and perspectives. Br J Ind Med 50:213–228

    Google Scholar 

  24. Van Oosterhout AJM, Ladenius ARC, Savelkoul HFJ, Van Ark I, Delsman KC, Nijkamp FP (1993) Effects of anti-IL-5 and IL-5 on airway hyperreactivity and eosinophils in guinea pigs. Am Rev Respir Dis 147:548–552

    Google Scholar 

  25. Zocca E, Fabbri LM, Boschetto P, Plebani M, Masiero M, Milani GF, Pivirotto F, Mapp CE (1990) Leukotriene B4 and late asthmatic reactions induced by toluene diisocyanate. J Appl Physiol 68:1576–1580

    Google Scholar 

Download references

Author information

Author notes

  1. M. Raulf

    Present address: Berufsgenossenschaftliches Forschungsinstitut fur Arbeitsmedizin (BGFA), Institut an der Ruhr-Universität Bochum, Bürkle-de-la-Camp-Platz 1, D-44789, Bochum 1, Germany

Authors and Affiliations

  1. Professional Associations' Research Institute for Occupational Medicine (BGFA), Institute at the Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, D-44789, Bochum 1, Germany

    M. Raulf, L. Tennie, B. Marczynski, J. Potthast, W. Marek & X. Baur

Authors
  1. M. Raulf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Tennie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Marczynski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Potthast
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W. Marek
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. X. Baur
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Results presented in the paper are part of the doctoral thesis of L. Tennie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Raulf, M., Tennie, L., Marczynski, B. et al. Cellular and mediator profile in bronchoalveolar lavage of guinea pigs after toluene diisocyanate (TDI) exposure. Lung 173, 57–68 (1995). https://doi.org/10.1007/BF00167601

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00167601

Key words

Search

Navigation