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. 1999;8(1):17–23. doi: 10.1080/09629359990676

Prevention of antigen-induced bronchial hyperreactivity and airway inflammation in sensitized guinea-pigs by tacrolimus.

J R Lapa e Silva 1, C Ruffié 1, J Lefort 1, M A Nahori 1, B B Vargaftig 1, M Pretolani 1
PMCID: PMC1781777  PMID: 10704085

Abstract

We examined the effect of the immunosuppressive agent, tacrolimus (FK506), on antigen-induced bronchial hyperreactivity to acetylcholine and leukocyte infiltration into the airways of ovalbumin-challenged guinea-pigs. Subcutaneous injection of 0.5 mg/kg of FK506, 1 h before and 5 h after intra-nasal antigen challenge prevented bronchial hyperreactivity to aerosolized acetylcholine, eosinophilia in bronchoalveolar lavage (BAL) fluid and bronchial tissue and the invasion of the bronchial wall by CD4+ T-lymphocytes. FK506 also suppressed ovalbumin-induced increase in the number of leukocytes adhering to the pulmonary vascular endothelium and expressing alpha4-integrins. Inhibition by FK506 of antigen-induced bronchial hyperreactivity in sensitized guinea-pigs may thus relate to its ability to prevent the emergence of important inflammatory components of airway inflammation, such as eosinophil accumulation, as well as CD4+ T-lymphocyte infiltration into the bronchial tissue.

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Selected References

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  1. Azzawi M., Bradley B., Jeffery P. K., Frew A. J., Wardlaw A. J., Knowles G., Assoufi B., Collins J. V., Durham S., Kay A. B. Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1407–1413. doi: 10.1164/ajrccm/142.6_Pt_1.1407. [DOI] [PubMed] [Google Scholar]
  2. Bishop D. K., Li W. Cyclosporin A and FK506 mediate differential effects on T cell activation in vivo. J Immunol. 1992 Feb 15;148(4):1049–1054. [PubMed] [Google Scholar]
  3. Bousquet J., Chanez P., Lacoste J. Y., Barnéon G., Ghavanian N., Enander I., Venge P., Ahlstedt S., Simony-Lafontaine J., Godard P. Eosinophilic inflammation in asthma. N Engl J Med. 1990 Oct 11;323(15):1033–1039. doi: 10.1056/NEJM199010113231505. [DOI] [PubMed] [Google Scholar]
  4. Corrigan C. J., Kay A. B. CD4 T-lymphocyte activation in acute severe asthma. Relationship to disease severity and atopic status. Am Rev Respir Dis. 1990 Apr;141(4 Pt 1):970–977. doi: 10.1164/ajrccm/141.4_Pt_1.. [DOI] [PubMed] [Google Scholar]
  5. Corrigan C. J., Kay A. B. T cells and eosinophils in the pathogenesis of asthma. Immunol Today. 1992 Dec;13(12):501–507. doi: 10.1016/0167-5699(92)90026-4. [DOI] [PubMed] [Google Scholar]
  6. Djukanović R., Roche W. R., Wilson J. W., Beasley C. R., Twentyman O. P., Howarth R. H., Holgate S. T. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. doi: 10.1164/ajrccm/142.2.434. [DOI] [PubMed] [Google Scholar]
  7. Gleich G. J., Loegering D. A., Maldonado J. E. Identification of a major basic protein in guinea pig eosinophil granules. J Exp Med. 1973 Jun 1;137(6):1459–1471. doi: 10.1084/jem.137.6.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hamid Q., Azzawi M., Ying S., Moqbel R., Wardlaw A. J., Corrigan C. J., Bradley B., Durham S. R., Collins J. V., Jeffery P. K. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest. 1991 May;87(5):1541–1546. doi: 10.1172/JCI115166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hatfield S. M., Roehm N. W. Cyclosporine and FK506 inhibition of murine mast cell cytokine production. J Pharmacol Exp Ther. 1992 Feb;260(2):680–688. [PubMed] [Google Scholar]
  10. Holgate S. T. The 1992 Cournand Lecture. Asthma: past, present and future. Eur Respir J. 1993 Nov;6(10):1507–1520. [PubMed] [Google Scholar]
  11. Hunt T. C., Summers J. A., Campos M. G., Rimmer S. J., Sturton G., Palfai S., Church M. K. Monoclonal antibodies specific for guinea pig eosinophil major basic protein: their use in an ELISA, immunocytochemistry and flow cytometry. Clin Exp Allergy. 1993 May;23(5):425–434. doi: 10.1111/j.1365-2222.1993.tb00349.x. [DOI] [PubMed] [Google Scholar]
  12. Jeffery P. K., Wardlaw A. J., Nelson F. C., Collins J. V., Kay A. B. Bronchial biopsies in asthma. An ultrastructural, quantitative study and correlation with hyperreactivity. Am Rev Respir Dis. 1989 Dec;140(6):1745–1753. doi: 10.1164/ajrccm/140.6.1745. [DOI] [PubMed] [Google Scholar]
  13. Kay A. B., Ying S., Varney V., Gaga M., Durham S. R., Moqbel R., Wardlaw A. J., Hamid Q. Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen-induced late-phase cutaneous reactions in atopic subjects. J Exp Med. 1991 Mar 1;173(3):775–778. doi: 10.1084/jem.173.3.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lefort J., Nahori M. A., Ruffie C., Vargaftig B. B., Pretolani M. In vivo neutralization of eosinophil-derived major basic protein inhibits antigen-induced bronchial hyperreactivity in sensitized guinea pigs. J Clin Invest. 1996 Feb 15;97(4):1117–1121. doi: 10.1172/JCI118505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lobb R. R., Hemler M. E. The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest. 1994 Nov;94(5):1722–1728. doi: 10.1172/JCI117519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lopez A. F., Elliott M. J., Woodcock J., Vadas M. A. GM-CSF, IL-3 and IL-5: cross-competition on human haemopoietic cells. Immunol Today. 1992 Dec;13(12):495–500. doi: 10.1016/0167-5699(92)90025-3. [DOI] [PubMed] [Google Scholar]
  17. Migita K., Eguchi K., Kawabe Y., Tsukada T., Mizokami A., Nagataki S. FK506 augments activation-induced programmed cell death of T lymphocytes in vivo. J Clin Invest. 1995 Aug;96(2):727–732. doi: 10.1172/JCI118116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nagai H., Yamaguchi S., Tanaka H., Inagaki N. Effect of some immunosuppressors on allergic bronchial inflammation and airway hyperresponsiveness in mice. Int Arch Allergy Immunol. 1995 Oct;108(2):189–195. doi: 10.1159/000237138. [DOI] [PubMed] [Google Scholar]
  19. Nakajima H., Iwamoto I., Tomoe S., Matsumura R., Tomioka H., Takatsu K., Yoshida S. CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. Am Rev Respir Dis. 1992 Aug;146(2):374–377. doi: 10.1164/ajrccm/146.2.374. [DOI] [PubMed] [Google Scholar]
  20. Nakata A., Kaminuma O., Mori A., Ogawa K., Kikkawa H., Naito K., Ikezawa K., Suko M., Okudaira H. Evidence that cyclosporin A and dexamethasone inhibit allergic airway eosinophilic inflammation via suppression of interleukin-5 synthesis by T cells. Br J Pharmacol. 1998 Aug;124(7):1425–1432. doi: 10.1038/sj.bjp.0701982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pober J. S., Lapierre L. A., Stolpen A. H., Brock T. A., Springer T. A., Fiers W., Bevilacqua M. P., Mendrick D. L., Gimbrone M. A., Jr Activation of cultured human endothelial cells by recombinant lymphotoxin: comparison with tumor necrosis factor and interleukin 1 species. J Immunol. 1987 May 15;138(10):3319–3324. [PubMed] [Google Scholar]
  22. Pretolani M., Lefort J., Vargaftig B. B. Active immunization induces lung hyperresponsiveness in the guinea pig. Pharmacologic modulation and triggering role of the booster injection. Am Rev Respir Dis. 1988 Dec;138(6):1572–1578. doi: 10.1164/ajrccm/138.6.1572. [DOI] [PubMed] [Google Scholar]
  23. Pretolani M., Ruffié C., Joseph D., Campos M. G., Church M. K., Lefort J., Vargaftig B. B. Role of eosinophil activation in the bronchial reactivity of allergic guinea pigs. Am J Respir Crit Care Med. 1994 May;149(5):1167–1174. doi: 10.1164/ajrccm.149.5.8173756. [DOI] [PubMed] [Google Scholar]
  24. Pretolani M., Ruffié C., Lapa e Silva J. R., Joseph D., Lobb R. R., Vargaftig B. B. Antibody to very late activation antigen 4 prevents antigen-induced bronchial hyperreactivity and cellular infiltration in the guinea pig airways. J Exp Med. 1994 Sep 1;180(3):795–805. doi: 10.1084/jem.180.3.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pretolani M., Vargaftig B. B. From lung hypersensitivity to bronchial hyperreactivity. What can we learn from studies on animal models? Biochem Pharmacol. 1993 Feb 24;45(4):791–800. doi: 10.1016/0006-2952(93)90161-o. [DOI] [PubMed] [Google Scholar]
  26. Pulido R., Elices M. J., Campanero M. R., Osborn L., Schiffer S., García-Pardo A., Lobb R., Hemler M. E., Sánchez-Madrid F. Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. Correlation with distinct alpha 4 epitopes. J Biol Chem. 1991 Jun 5;266(16):10241–10245. [PubMed] [Google Scholar]
  27. Robinson D. S., Hamid Q., Ying S., Tsicopoulos A., Barkans J., Bentley A. M., Corrigan C., Durham S. R., Kay A. B. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992 Jan 30;326(5):298–304. doi: 10.1056/NEJM199201303260504. [DOI] [PubMed] [Google Scholar]
  28. Schäfer H., Burger R. Identification and functional characterization of guinea-pig CD4: antibody binding transduces a negative signal on T-cell activation. Immunology. 1991 Feb;72(2):261–268. [PMC free article] [PubMed] [Google Scholar]
  29. Tan B. T., Ekelaar F., Luirink J., Rimmelzwaan G., De Jonge A. J., Scheper R. J. Production of monoclonal antibodies defining guinea pig T-cell surface markers and a strain 13 Ia-like antigen: the value of immunohistological screening. Hybridoma. 1985 Summer;4(2):115–124. doi: 10.1089/hyb.1985.4.115. [DOI] [PubMed] [Google Scholar]
  30. Thornhill M. H., Haskard D. O. IL-4 regulates endothelial cell activation by IL-1, tumor necrosis factor, or IFN-gamma. J Immunol. 1990 Aug 1;145(3):865–872. [PubMed] [Google Scholar]
  31. Weg V. B., Williams T. J., Lobb R. R., Nourshargh S. A monoclonal antibody recognizing very late activation antigen-4 inhibits eosinophil accumulation in vivo. J Exp Med. 1993 Feb 1;177(2):561–566. doi: 10.1084/jem.177.2.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wegner C. D., Gundel R. H., Reilly P., Haynes N., Letts L. G., Rothlein R. Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science. 1990 Jan 26;247(4941):456–459. doi: 10.1126/science.1967851. [DOI] [PubMed] [Google Scholar]
  33. Zucker-Franklin D., Grusky G. The identification of eosinophil colonies in soft-agar cultures by differential staining for peroxidase. J Histochem Cytochem. 1976 Dec;24(12):1270–1272. doi: 10.1177/24.12.63511. [DOI] [PubMed] [Google Scholar]
  34. de Paulis A., Cirillo R., Ciccarelli A., de Crescenzo G., Oriente A., Marone G. Characterization of the anti-inflammatory effect of FK-506 on human mast cells. J Immunol. 1991 Dec 15;147(12):4278–4285. [PubMed] [Google Scholar]

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