Skip to main content
SpringerLink
Log in

Lung lymphocytes in bleomycin-induced pulmonary disease

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Previous studies have not clearly defined the role of cell-mediated immunity in bleomycin-induced lung injury. In this report the functional activity of T lymphocytes obtained from minced lung preparations, bronchoalveolar lavage, and blood of rabbits treated with bleomycin was examined in cell proliferation and cell-mediated cytotoxicity assays. Four days after instillation of bleomycin (10 units/kg) into the right lung, histologic examination revealed mononuclear cell interstitial infiltrates and alveolar exudates. Right lung bronchoalveolar lavage (BAL) cell counts were similar in both groups, but the percentage of lymphocytes and neutrophils was elevated in bleomycin-treated groups (25% vs. 7% and 35% vs. 0% respectively;p<0.05). Spontaneous proliferation of cultured BAL and blood lymphocytes was similar in bleomycin-treated rabbits and controls. After 24 h of incubation with interleukin-2 (IL-2), BAL lymphocytes from bleomycin-treated rabbits had nearly a 4-fold greater proliferative response than lymphocytes from untreated rabbits. Concanavalin-A-dependent cell-mediated cytotoxicity (CDCMC) assays were performed to evaluate cytolytic lymphocyte activity. Spontaneous CDCMC activity was not detected in BAL fluid or in blood lymphocytes from either treated or control animals. After 24 h of incubation with IL-2, significant CDCMC activity was detected in lung lymphocytes from bleomycin-treated animals, but not in lung lymphocytes from control animals. These results indicate that stimulated lymphocytes are present in the lungs of rabbits 4 days after exposure to bleomycin.

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. Adamson IYR, Bouden DH (1979) The pathogenesis of bleomycin induced pulmonary fibrosis in mice. Am J Pathol 95:117–127

    Google Scholar 

  2. Aso Y, Yoneda K, Kikkawa Y (1976) Morphologic and biochemical study of pulmonary changes induced by bleomycin in mice. Lab Invest 35:558–568

    PubMed  CAS  Google Scholar 

  3. Catravas JL, Lazo JS, Doubler KJ, Mills LR, Gillis CN (1983) Pulmonary endothelial dysfunction in the presence or absence of interstitial injury induced by intratracheally injected bleomycin in rabbits. Am Rev Respir Dis 128:740–746

    PubMed  CAS  Google Scholar 

  4. Cooper JAD Jr, White DA, Matthay R (1986) Drug-induced Pulmonary Disease. Part 1: Cytotoxic Drugs. Am Rev Respir Dis 133:321–340

    PubMed  CAS  Google Scholar 

  5. Emeson EE, Norin AJ, Veith FJ (1982) Lectin dependent cell mediated cytotoxicity. A new simple method to quantitate cytotoxic T cell activity in dogs. Transplantation 33:261–270

    Article  Google Scholar 

  6. Greaves MF, Brown GJ (1974) Purification of human T and B Lymphocytes. J Immunol 112:420–423

    PubMed  CAS  Google Scholar 

  7. Grimm EA, Mazumdi A, Zhang HZ, and Rosenberg SA (1982) Lymphokine activated killer cell phenomena. Lysis of natural killer resistant fresh solid tumor cells by Interleukin-2 activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823–1941

    Article  PubMed  CAS  Google Scholar 

  8. Lazo JS, Catravas JD, Gillis CN (1981) Reduction in rabbit serum and pulmonary angiotensin converting enzyme after subacute bleomycin treatment. Biochem Pharmacol 18:2577–2584

    Article  Google Scholar 

  9. Ling NR, Kay JE (1975) Lymphocyte stimulation. American Elsevier Publishing, New York

    Google Scholar 

  10. Neubauer RH, Brown RL, Kawalkami TG (1981) Spontaneous release of a factor with properties of T-cell growth factor from a continuous line of primate tumor cells. Immunology 127:1852–1856

    Google Scholar 

  11. Norin AJ, Kamholz SL, Pinsker KL, Emeson EE (1986) Concanvalin A dependent cell mediated cytotoxicity in bronchoalveolar lavage fluid. Correlation with lung allograft. Transplantation 42:466–472.

    Article  PubMed  CAS  Google Scholar 

  12. Norin AJ, Kamholz SL, Pinsker KL, Emeson EE, Veith FJ (1987) Cyclosporine-induced tolerance in experimental organ transplantation: evidence of diminished donor-specific proliferative response. J Immunol 139:332–337

    PubMed  CAS  Google Scholar 

  13. Norin AJ, Karpel JP, Fleitman J, Kamholz S, Pinsker K (1986) Concanavalin A dependent cell-mediated cytoxocity (CDCMC) in bronchoalveolar lavage (BAL) fluid of patients with interstitial lung disease (ILD). Evidence of cytolytic T-lymphocyte (CTL) activity. Chest 89:144s-145s

    PubMed  CAS  Google Scholar 

  14. Phan SH, Thrall RS, Williams C (1981) Bleomycin-induced pulmonary fibrosis. Effects of steroid on lung collagen metabolism. Am Rev Respir Dis 124:428–434

    PubMed  CAS  Google Scholar 

  15. Philips JH, Lanier LL (1986) Lectin-dependent and anti-CD3 induced cytotoxicity are preferentially mediated by peripheral blood cytotoxic T lymphocytes expressing Leu-7 antigen. J Immunol 136:1579–1585

    Google Scholar 

  16. Schrier DJ, Phan SH (1984) Modulation of bleomycin-induced pulmonary fibrosis in the BABL/c Mouse by cyclophosphamide-sensitive T cells. Am J Pathol 116:270–278

    PubMed  CAS  Google Scholar 

  17. Schrier DJ, Phan SH, McGarry BM (1983) The effect of the nude mutation (nu/nu) on bleomycin-induced pulmonary fibrosis. A biochemical evaluation. Am Rev Respir Dis 127:614–617

    PubMed  CAS  Google Scholar 

  18. Snider GL, Celli BR, Goldstein RH, O’Brien JJ, Lucey EC (1978) Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin. Am Rev Respir Dis 117:289–297

    PubMed  CAS  Google Scholar 

  19. Szapiel SV, Elson NA, Fulmer JD, Hunninghake GW, Crystal RG (1979) Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis 120:893–889.

    PubMed  CAS  Google Scholar 

  20. Thrall RS, McCormick JR, Phan SH, Jack RH, Ward PA (1979) The effect of anti-lymphocyte globulin on the development of bleomycin-induced pulmonary fibrosis in the rat (abstract). Am Rev Respir Dis 19 (suppl. 83)

    Google Scholar 

  21. Thrall RS, Barton RW, D’Amato DA, Sulavik SB (1982) Differential cellular analysis of bronchoalveolar lavage fluid obtained at various stages during the development of bleomycin-induced pulmonary fibrosis in the rat. Am Rev Respir Dis 126:488–492

    PubMed  CAS  Google Scholar 

  22. Thrall RS, Barton RW (1984) A comparison of lymphocyte populations in the lung tissue and in bronchoalveolar lavage fluid of rats various times during the development of bleomycin-induced pulmonary fibrosis. Am Rev Respir Dis 129:279–283

    PubMed  CAS  Google Scholar 

  23. Thrall RS, Lovett EJ, Barton RW, McCormick JR, Phan SH, Ward PA (1980) The effect of T-cell depletion on the development of bleomycin-induced pulmonary fibrosis in the rat. Am Rev Respir Dis 121 (suppl. 99)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Medicine, Pathology, Microbiology, and Immunology, and Surgery, Montefiore Medical Center, North Central Bronx Hospital Center, Albert Einstein College of Medicine, USA, Bronx, New York

    Jill P. Karpel, Thomas K. Aldrich, Sumi Mitsudo & Allen J. Norin

Authors
  1. Jill P. Karpel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas K. Aldrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sumi Mitsudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Allen J. Norin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karpel, J.P., Aldrich, T.K., Mitsudo, S. et al. Lung lymphocytes in bleomycin-induced pulmonary disease. Lung 167, 163–172 (1989). https://doi.org/10.1007/BF02714945

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02714945

Key words

Search

Navigation