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. 1974 Jul 1;140(1):105–125. doi: 10.1084/jem.140.1.105

EXPERIMENTAL IMMUNE COMPLEX DISEASE OF THE LUNG

THE PATHOGENESIS OF A LABORATORY MODEL RESEMBLING CERTAIN HUMAN INTERSTITIAL LUNG DISEASES

Jan R Brentjens 1, David W O'Connell 1, Irene B Pawlowski 1, Konrad C Hsu 1, Giuseppe A Andres 1
PMCID: PMC2139706  PMID: 4275830

Abstract

Membranous and/or proliferative pneumonitis, similar in certain features to human interstitial pneumonitis, developed in rabbits making hyperactive antibody response to daily injections of bovine serum albumin (BSA) administered in multiple large doses sufficient to maintain the state of relative antigen-antibody equivalence. The pulmonary lesions were associated with deposition in alveolar capillary walls and interstitium of antigen, host globulin and complement, presumably in immune complexes. In some rabbits chronic interstitial pneumonitis, characterized by thickening of alveolar capillary walls, interstitial fibrosis and deposition of fibrinogen, was observed. The production of immune complex pneumonitis seems to depend on the degree of the antibody response because rabbits developing chronic serum sickness with low doses of BSA, rabbits with acute serum sickness as well as nonresponders showed no pulmonary alterations. This observation is comparable to that described by Dixon in his studies on experimental immune complex glomerulonephritis. It is conceivable that the pulmonary pathology shown here is produced by formation of larger amounts of complexes which may persist longer at critical levels in the circulation than in rabbits immunized with a single daily injection of BSA. In conclusion this study suggests: first, that experimental chronic serum sickness can be used as a model, not only for glomerulonephritis, but also for experimental systemic disease, comparable to human systemic diseases produced by circulating antigen-antibody complexes; and second, that the pathogenesis proposed here offers an alternative to using antilung basement membrane pneumonitis for the experimental approach to the study of human lung immunopathology.

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Selected References

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  1. ANDRES G. A., SEEGAL B. C., HSU K. C., ROTHENBERG M. S., CHAPEAU M. L. Electron microscopic studies of experimental nephritis with ferritin-conjugated antibody. Localization of antigen-antibody complexes in rabbit glomeruli following repeated injections of bovine serum albumin. J Exp Med. 1963 Apr 1;117:691–704. doi: 10.1084/jem.117.4.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andres G. A., Accinni L., Beiser S. M., Christian C. L., Cinotti G. A., Erlanger B. F., Hsu K. C., Seegal B. C. Localization of fluorescein-labeled antinucleoside antibodies in glomeruli of patients with active systemic lupus erythematosus nephritis. J Clin Invest. 1970 Nov;49(11):2106–2118. doi: 10.1172/JCI106428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cochrane C. G. Mechanisms involved in the deposition of immune complexes in tissues. J Exp Med. 1971 Sep 1;134(3 Pt 2):75s–89s. [PubMed] [Google Scholar]
  4. DIXON F. J., FELDMAN J. D., VAZQUEZ J. J. Experimental glomerulonephritis. The pathogenesis of a laboratory model resembling the spectrum of human glomerulonephritis. J Exp Med. 1961 May 1;113:899–920. doi: 10.1084/jem.113.5.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eisenberg H., Dubois E. L., Sherwin R. P., Balchum O. J. Diffuse interstitial lung disease in systemic lupus erythematosus. Ann Intern Med. 1973 Jul;79(1):37–45. doi: 10.7326/0003-4819-79-1-37. [DOI] [PubMed] [Google Scholar]
  6. Elliott M. L., Kuhn C. Idiopathic pulmonary hemosiderosis. Ultrastructural abnormalities in the capillary walls. Am Rev Respir Dis. 1970 Dec;102(6):895–904. doi: 10.1164/arrd.1970.102.6.895. [DOI] [PubMed] [Google Scholar]
  7. Földes I., Beregi E. Immunomorphological methods in the diagnosis of lung diseases. Scand J Respir Dis Suppl. 1972;80:73–80. [PubMed] [Google Scholar]
  8. HUANG C. T., HENNIGAR G. R., LYONS H. A. PULMONARY DYSFUNCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS. N Engl J Med. 1965 Feb 11;272:288–293. doi: 10.1056/NEJM196502112720604. [DOI] [PubMed] [Google Scholar]
  9. Hagadorn J. E., Vazquez J. J., Kinney T. R. Immunopathologic studies of an experimental model resembling Goodpasture's syndrome. Am J Pathol. 1969 Oct;57(1):17–30. [PMC free article] [PubMed] [Google Scholar]
  10. Kapanci Y., Chamay A. Lésions en anse de fil de fer des capillaires pulmonaires dans le lupus érythemateux disseminé (L.E.D.) Virchows Arch Pathol Anat Physiol Klin Med. 1967 Jun 12;342(3):236–243. [PubMed] [Google Scholar]
  11. Koffler D., Sandson J., Carr R., Kunkel H. G. Immunologic studies concerning the pulmonary lesions in Goodpasture's syndrome. Am J Pathol. 1969 Feb;54(2):293–305. [PMC free article] [PubMed] [Google Scholar]
  12. Koffler D., Schur P. H., Kunkel H. G. Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med. 1967 Oct 1;126(4):607–624. doi: 10.1084/jem.126.4.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kuhn C. Systemic lupus erythematosus in a patient with ultrastructural lesions of the pulmonary capillaries previously reported in the review as due to idiopathic pulmonary hemosiderosis. Am Rev Respir Dis. 1972 Dec;106(6):931–932. doi: 10.1164/arrd.1972.106.6.931a. [DOI] [PubMed] [Google Scholar]
  14. Levin D. C. Proper interpretation of pulmonary roentgen changes in systemic lupus erythematosus. Am J Roentgenol Radium Ther Nucl Med. 1971 Mar;111(3):510–517. doi: 10.2214/ajr.111.3.510. [DOI] [PubMed] [Google Scholar]
  15. Lewis E. J., Schur P. H., Busch G. J., Galvanek E., Merrill J. P. Immunopathologic features of a patient with glomerulonephritis and pulmonary hemorrhage. Am J Med. 1973 Apr;54(4):507–513. doi: 10.1016/0002-9343(73)90046-6. [DOI] [PubMed] [Google Scholar]
  16. MOERSCH H. J., PURNELL D. C., GOOD C. A. Pulmonary changes occurring in disseminated lupus erythematosus. Dis Chest. 1956 Feb;29(2):166–173. doi: 10.1378/chest.29.2.166. [DOI] [PubMed] [Google Scholar]
  17. McCombs R. P. Diseases due to immunologic reactions in the lungs (first of two parts). N Engl J Med. 1972 Jun 1;286(22):1186–1194. doi: 10.1056/NEJM197206012862205. [DOI] [PubMed] [Google Scholar]
  18. McKINNON G. E., ANDREWS E. C., Jr, HEPTINSTALL R. H., GERMUTH F. G., Jr An immunohistologic study on the occurrence of intravascular antigen-antibody precipitation and its role in anaphylaxis in the rabbit. Bull Johns Hopkins Hosp. 1957 Nov;101(5):258–280. [PubMed] [Google Scholar]
  19. NASTUK W. L., PLESCIA O. J., OSSERMAN K. E. Changes in serum complement activity in patients with myasthenia gravis. Proc Soc Exp Biol Med. 1960 Oct;105:177–184. doi: 10.3181/00379727-105-26050. [DOI] [PubMed] [Google Scholar]
  20. Nozawa Y. Histopathological findings of the lung in collagen diseases--especially on their differential diagnosis. Acta Pathol Jpn. 1972 Nov;22(4):843–858. doi: 10.1111/j.1440-1827.1972.tb00767.x. [DOI] [PubMed] [Google Scholar]
  21. Siegenthaler R., Hedinger C. Massive Lungenhämosiderose bei Lupus erythematodes disseminatus. Schweiz Med Wochenschr. 1966 Oct 8;96(40):1323–1331. [PubMed] [Google Scholar]
  22. Sperryn P. N., Mace B. E. Systemic lupus erythematosus with fibrosing alveolitis. Proc R Soc Med. 1971 Jan;64(1):58–59. doi: 10.1177/003591577106400135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sturgill B. C., Westervelt F. B. Immunofluorescence studies in a case of Goodpasture's syndrome. JAMA. 1965 Nov 22;194(8):914–916. [PubMed] [Google Scholar]
  24. TOMASI T. B., Jr, FUDENBERG H. H., FINBY N. Possible relationship of rheumatoid factors and pulmonary disease. Am J Med. 1962 Aug;33:243–248. doi: 10.1016/0002-9343(62)90022-0. [DOI] [PubMed] [Google Scholar]
  25. Vazquez J. J. Immunopathologic aspects of lung disease. Arch Intern Med. 1970 Sep;126(3):471–474. [PubMed] [Google Scholar]
  26. WEIGLE W. O., COCHRANE C. G., DIXON F. J. Anaphylactogenic properties of soluble antigen-antibody complexes in the guinea pig and rabbit. J Immunol. 1960 Nov;85:469–477. [PubMed] [Google Scholar]
  27. Willoughby W. F., Dixon F. J. Experimental hemorrhagic pneumonitis produced by heterologous anti-lung antibody. J Immunol. 1970 Jan;104(1):28–37. [PubMed] [Google Scholar]

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