Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1987 Aug;42(8):565–572. doi: 10.1136/thx.42.8.565

Role of mast cells in the pathogenesis of hypersensitivity pneumonitis.

P Soler 1, S Nioche 1, D Valeyre 1, F Basset 1, J Benveniste 1, C Burtin 1, J P Battesti 1, R Georges 1, A J Hance 1
PMCID: PMC460853  PMID: 3499002

Abstract

To examine the possibility that mast cells have a central role in the pathogenesis of hypersensitivity pneumonitis, 20 patients with this disease were studied with the aim of seeking evidence for mast cell degranulation. The number of mast cells recovered by bronchoalveolar lavage from patients with hypersensitivity pneumonitis was more than 1,000 times greater than those recovered from normal individuals. Furthermore, discontinuation of antigen exposure resulted in an increase in the number of mast cells observed, consistent with the possibility that antigen exposure had induced mast cell degranulation. Cessation of antigen exposure also resulted in a rapid decrease in the number of neutrophils and eosinophils recovered by lavage, followed by an increase in the number of T8+ T lymphocytes present. In each case the time course of the changes was consistent with the possibility that mast cell degranulation had been important in regulating the number of the immune and inflammatory cells present in the lung. Histamine was present in lavage fluid supernatant from patients with hypersensitivity pneumonitis. The amount of histamine present was, however, closely correlated with the number of mast cells present and not with the interval since last antigen exposure. Delay in separating cells from lavage fluid supernatant resulted in an increase in histamine content. These results suggest that the free histamine in lavage fluid resulted from the degranulation of mast cells induced by the lavage procedure as histamine released in vivo has a short half life. We suggest that hypersensitivity pneumonitis results from a "late phase reaction" initiated by antigen induced mast cell degranulation.

Full text

PDF
565

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agius R. M., Godfrey R. C., Holgate S. T. Mast cell and histamine content of human bronchoalveolar lavage fluid. Thorax. 1985 Oct;40(10):760–767. doi: 10.1136/thx.40.10.760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Basset F., Ferrans V. J., Soler P., Takemura T., Fukuda Y., Crystal R. G. Intraluminal fibrosis in interstitial lung disorders. Am J Pathol. 1986 Mar;122(3):443–461. [PMC free article] [PubMed] [Google Scholar]
  3. Baur X., Dorsch W., Becker T. Levels of complement factors in human serum during immediate and late asthmatic reactions and during acute hypersensitivity pneumonitis. Allergy. 1980 Jul;35(5):383–390. doi: 10.1111/j.1398-9995.1980.tb01783.x. [DOI] [PubMed] [Google Scholar]
  4. Chollet S., Soler P., Dournovo P., Richard M. S., Ferrans V. J., Basset F. Diagnosis of pulmonary histiocytosis X by immunodetection of Langerhans cells in bronchoalveolar lavage fluid. Am J Pathol. 1984 May;115(2):225–232. [PMC free article] [PubMed] [Google Scholar]
  5. Cormier Y., Bélanger J., Beaudoin J., Laviolette M., Beaudoin R., Hebert J. Abnormal bronchoalveolar lavage in asymptomatic dairy farmers. Study of lymphocytes. Am Rev Respir Dis. 1984 Dec;130(6):1046–1049. doi: 10.1164/arrd.1984.130.6.1046. [DOI] [PubMed] [Google Scholar]
  6. Costabel U., Bross K. J., Marxen J., Matthys H. T-lymphocytosis in bronchoalveolar lavage fluid of hypersensitivity pneumonitis. Changes in profile of T-cell subsets during the course of disease. Chest. 1984 Apr;85(4):514–522. doi: 10.1378/chest.85.4.514. [DOI] [PubMed] [Google Scholar]
  7. Daniele R. P., Henson P. M., Fantone J. C., 3rd, Ward P. A., Dreisin R. B. Immune complex injury of the lung. Symposium held at the 74th annual meeting of the American Thoracic Society, Las Vegas, Nevada, May 1979. Am Rev Respir Dis. 1981 Dec;124(6):738–755. [PubMed] [Google Scholar]
  8. Dvorak A. M., Galli S. J., Morgan E., Galli A. S., Hammond M. E., Dvorak H. F. Anaphylactic degranulation of guinea pig basophilic leukocytes. II. Evidence for regranulation of mature basophils during recovery from degranulation in vitro. Lab Invest. 1982 May;46(5):461–475. [PubMed] [Google Scholar]
  9. Fink J. N. Hypersensitivity pneumonitis. J Allergy Clin Immunol. 1984 Jul;74(1):1–10. doi: 10.1016/0091-6749(84)90077-0. [DOI] [PubMed] [Google Scholar]
  10. Fink J. N., Moore V. L., Barboriak J. J. Cell-mediated hypersensitivity in pigeon breeders. Int Arch Allergy Appl Immunol. 1975;49(6):831–836. doi: 10.1159/000231466. [DOI] [PubMed] [Google Scholar]
  11. Fournier E., Tonnel A. B., Gosset P., Wallaert B., Ameisen J. C., Voisin C. Early neutrophil alveolitis after antigen inhalation in hypersensitivity pneumonitis. Chest. 1985 Oct;88(4):563–566. doi: 10.1378/chest.88.4.563. [DOI] [PubMed] [Google Scholar]
  12. Georges R., Saumon G., Loiseau A. The relationship of age to pulmonary membrane conductance and capillary blood volume. Am Rev Respir Dis. 1978 Jun;117(6):1069–1078. doi: 10.1164/arrd.1978.117.6.1069. [DOI] [PubMed] [Google Scholar]
  13. Ghose T., Landrigan P., Killeen R., Dill J. Immunopathological studies in patients with farmer's lung. Clin Allergy. 1974 Jun;4(2):119–129. doi: 10.1111/j.1365-2222.1974.tb01369.x. [DOI] [PubMed] [Google Scholar]
  14. Kaliner M., Lemanske R. Inflammatory responses to mast cell granules. Fed Proc. 1984 Oct;43(13):2846–2851. [PubMed] [Google Scholar]
  15. Keller R. H., Swartz S., Schlueter D. P., Bar-Sela S., Fink J. N. Immunoregulation in hypersensitivity pneumonitis: phenotypic and functional studies of bronchoalveolar lavage lymphocytes. Am Rev Respir Dis. 1984 Nov;130(5):766–771. doi: 10.1164/arrd.1984.130.5.766. [DOI] [PubMed] [Google Scholar]
  16. Khan M. M., Sansoni P., Engleman E. G., Melmon K. L. Pharmacologic effects of autacoids on subsets of T cells. Regulation of expression/function of histamine-2 receptors by a subset of suppressor cells. J Clin Invest. 1985 May;75(5):1578–1583. doi: 10.1172/JCI111863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Larsen G. L. Hypersensitivity lung disease. Annu Rev Immunol. 1985;3:59–85. doi: 10.1146/annurev.iy.03.040185.000423. [DOI] [PubMed] [Google Scholar]
  18. Leatherman J. W., Michael A. F., Schwartz B. A., Hoidal J. R. Lung T cells in hypersensitivity pneumonitis. Ann Intern Med. 1984 Mar;100(3):390–392. doi: 10.7326/0003-4819-100-3-390. [DOI] [PubMed] [Google Scholar]
  19. Lebel B. A high-sampling-rate automated continuous-flow fluorometric technique for the analysis of nanogram levels of histamine in biological samples. Anal Biochem. 1983 Aug;133(1):16–29. doi: 10.1016/0003-2697(83)90217-8. [DOI] [PubMed] [Google Scholar]
  20. Moore V. L., Fink J. N., Barboriak J. J., Ruff L. L., Schlueter D. P. Immunologic events in pigeon breeders' disease. J Allergy Clin Immunol. 1974 Jun;53(6):319–328. doi: 10.1016/0091-6749(74)90115-8. [DOI] [PubMed] [Google Scholar]
  21. Moore V. L., Fink J. N., Barboriak J. J., Ruff L. L., Schlueter D. P. Immunologic events in pigeon breeders' disease. J Allergy Clin Immunol. 1974 Jun;53(6):319–328. doi: 10.1016/0091-6749(74)90115-8. [DOI] [PubMed] [Google Scholar]
  22. Mornex J. F., Cordier G., Pages J., Vergnon J. M., Lefebvre R., Brune J., Revillard J. P. Activated lung lymphocytes in hypersensitivity pneumonitis. J Allergy Clin Immunol. 1984 Nov;74(5):719–727. doi: 10.1016/0091-6749(84)90236-7. [DOI] [PubMed] [Google Scholar]
  23. Murphy K. R., Wilson M. C., Irvin C. G., Glezen L. S., Marsh W. R., Haslett C., Henson P. M., Larsen G. L. The requirement for polymorphonuclear leukocytes in the late asthmatic response and heightened airways reactivity in an animal model. Am Rev Respir Dis. 1986 Jul;134(1):62–68. doi: 10.1164/arrd.1986.134.1.62. [DOI] [PubMed] [Google Scholar]
  24. Naclerio R. M., Proud D., Togias A. G., Adkinson N. F., Jr, Meyers D. A., Kagey-Sobotka A., Plaut M., Norman P. S., Lichtenstein L. M. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med. 1985 Jul 11;313(2):65–70. doi: 10.1056/NEJM198507113130201. [DOI] [PubMed] [Google Scholar]
  25. Nagy L., Lee T. H., Kay A. B. Neutrophil chemotactic activity in antigen-induced late asthmatic reactions. N Engl J Med. 1982 Mar 4;306(9):497–501. doi: 10.1056/NEJM198203043060901. [DOI] [PubMed] [Google Scholar]
  26. Pepys J. Hypersensitivity diseases of the lungs due to fungi and organic dusts. Monogr Allergy. 1969;4:1–147. [PubMed] [Google Scholar]
  27. Reyes C. N., Wenzel F. J., Lawton B. R., Emanuel D. A. The pulmonary pathology of farmer's lung disease. Chest. 1982 Feb;81(2):142–146. doi: 10.1378/chest.81.2.142. [DOI] [PubMed] [Google Scholar]
  28. Reynolds H. Y., Fulmer J. D., Kazmierowski J. A., Roberts W. C., Frank M. M., Crystal R. G. Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. J Clin Invest. 1977 Jan;59(1):165–175. doi: 10.1172/JCI108615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Salvaggio J. E., deShazo R. D. Pathogenesis of hypersensitivity pneumonitis. Chest. 1986 Mar;89(3 Suppl):190S–193S. doi: 10.1378/chest.89.3_supplement.190s. [DOI] [PubMed] [Google Scholar]
  30. Sansoni P., Silverman E. D., Khan M. M., Melmon K. L., Engleman E. G. Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells. J Clin Invest. 1985 Feb;75(2):650–656. doi: 10.1172/JCI111743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schwartz L. B., Austen K. F. Structure and function of the chemical mediators of mast cells. Prog Allergy. 1984;34:271–321. [PubMed] [Google Scholar]
  32. Weil B. J., Renoux M. L. Study of granule reappearance and histamine synthesis in rat mast cells maintained in short-term cultures. Cell Immunol. 1982 Apr;68(2):220–233. doi: 10.1016/0008-8749(82)90107-1. [DOI] [PubMed] [Google Scholar]
  33. Wenzel F. J., Emanuel D. A., Gray R. L. Immunofluorescent studies in patients with farmer's lung. J Allergy Clin Immunol. 1971 Oct;48(4):224–229. doi: 10.1016/0091-6749(71)90069-8. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES