Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1987 Nov;129(2):277–286.

Pathogenesis of bronchiolitis and pneumonia induced in neonatal and weanling rats by parainfluenza (Sendai) virus.

W L Castleman 1, L J Brundage-Anguish 1, L Kreitzer 1, S B Neuenschwander 1
PMCID: PMC1899730  PMID: 2823613

Abstract

The objective of this research was to identify potential mechanisms that might account for the greater susceptibility of neonatal rats (5 days old) as compared with weanling rats (25 days old) to viral-induced lung injury. Sites of viral replication, the sequential development of bronchiolitis and pneumonia, and systemic humoral immune responses were compared between neonatal and weanling rats from 2 to 17 days after being inoculated intranasally with parainfluenza Type 1 (Sendai) virus. In both neonatal and weanling rats, viral antigen was demonstrated by immunoperoxidase technique and viral nucleocapsids, and budding virions were demonstrated by transmission electron microscopy in bronchiolar ciliated and nonciliated epithelial cells as early as 2 days after inoculation. Similar evidence of viral replication was also demonstrated in both ages of rats in alveolar Type I and Type II epithelial cells and in macrophages. Neither virus nor viral antigens was identified in endothelial cells or interstitial cells of interalveolar septa. Bronchiolitis was induced as early as 2 days after inoculation in both ages of rats and was characterized by necrosis, erosion, and hyperplasia of epithelial cells. Multifocal to locally extensive interstitial pneumonia centered on bronchioles, was characterized by alveolar epithelial cell damage and by infiltration of neutrophils, macrophages, and lymphocytes in alveolar septa and spaces and was observed as early as 2 days after inoculation in both age groups of rats. Interstitial pneumonia of maximal severity occurred in weanling rats at 5 days after inoculation, whereas maximal pneumonia of comparable severity occurred in neonatal rats at 8 days after inoculation. Epithelial repair and resolution of bronchiolitis and pneumonia were largely complete in both ages of rats by 17 days after inoculation. Virus was recovered from lung homogenates of neonatal and weanling rats as early as 2 days after inoculation. In weanling rats, infective virus could not be recovered from lung beyond 6 days after inoculation, whereas in neonatal rats virus could be recovered from lung as late as 10 days after inoculation. Viral persistence in neonatal rats was associated with a delayed onset of serum antibody to the virus, compared with weanling rats. The results indicate that the cellular sites of viral replication and the pattern of inflammatory reactions are closely comparable between neonatal and weanling rats inoculated with Sendai virus.(ABSTRACT TRUNCATED AT 400 WORDS)

Full text

PDF
277

Images in this article

281Figure 3
on p.281
281Figure 4
on p.281
282Figure 6
on p.282
282Figure 7
on p.282
283Figure 8
on p.283
283Figure 9
on p.283
283Figure 10
on p.283
283Figure 11
on p.283

Selected References

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

  1. Aherne W., Bird T., Court S. D., Gardner P. S., McQuillin J. Pathological changes in virus infections of the lower respiratory tract in children. J Clin Pathol. 1970 Feb;23(1):7–18. doi: 10.1136/jcp.23.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Angle M. J., McManus L. M., Pinckard R. N. Age-dependent differential development of leukotactic and vasoactive responsiveness to acute inflammatory mediators. Lab Invest. 1986 Dec;55(6):616–621. [PubMed] [Google Scholar]
  3. Becroft D. M. Histopathology of fatal adenovirus infection of the respiratory tract in young children. J Clin Pathol. 1967 Jul;20(4):561–569. doi: 10.1136/jcp.20.4.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brody J. S., Kaplan N. B. Proliferation of alveolar interstitial cells during postnatal lung growth. Evidence for two distinct populations of pulmonary fibroblasts. Am Rev Respir Dis. 1983 Jun;127(6):763–770. doi: 10.1164/arrd.1983.127.6.763. [DOI] [PubMed] [Google Scholar]
  5. Brownstein D. G., Smith A. L., Johnson E. A. Sendai virus infection in genetically resistant and susceptible mice. Am J Pathol. 1981 Nov;105(2):156–163. [PMC free article] [PubMed] [Google Scholar]
  6. Burri P. H., Dbaly J., Weibel E. R. The postnatal growth of the rat lung. I. Morphometry. Anat Rec. 1974 Apr;178(4):711–730. doi: 10.1002/ar.1091780405. [DOI] [PubMed] [Google Scholar]
  7. Burrows B., Knudson R. J., Lebowitz M. D. The relationship of childhood respiratory illness to adult obstructive airway disease. Am Rev Respir Dis. 1977 May;115(5):751–760. doi: 10.1164/arrd.1977.115.5.751. [DOI] [PubMed] [Google Scholar]
  8. Castleman W. L. Alterations in pulmonary ultrastructure and morphometric parameters induced by parainfluenza (Sendai) virus in rats during postnatal growth. Am J Pathol. 1984 Feb;114(2):322–335. [PMC free article] [PubMed] [Google Scholar]
  9. Castleman W. L. Bronchiolitis obliterans and pneumonia induced in young dogs by experimental adenovirus infection. Am J Pathol. 1985 Jun;119(3):495–504. [PMC free article] [PubMed] [Google Scholar]
  10. Castleman W. L., Dungworth D. L., Schwartz L. W., Tyler W. S. Acute respiratory bronchiolitis: an ultrastructural and autoradiographic study of epithelial cell injury and renewal in rhesus monkeys exposed to ozone. Am J Pathol. 1980 Mar;98(3):811–840. [PMC free article] [PubMed] [Google Scholar]
  11. Cheung A. T., Kurland G., Miller M. E., Ford E. W., Ayin S. A., Walsh E. M. Host defense deficiency in newborn nonhuman primate lungs. J Med Primatol. 1986;15(1):37–47. [PubMed] [Google Scholar]
  12. Choppin P. W., Scheid A. The role of viral glycoproteins in adsorption, penetration, and pathogenicity of viruses. Rev Infect Dis. 1980 Jan-Feb;2(1):40–61. doi: 10.1093/clinids/2.1.40. [DOI] [PubMed] [Google Scholar]
  13. Coates D. M., Husseini R. H., Collie M. H., Sweet C., Smith H. The role of cellular susceptibility in the declining severity of respiratory influenza of ferrets with age. Br J Exp Pathol. 1984 Feb;65(1):29–39. [PMC free article] [PubMed] [Google Scholar]
  14. Collier A. M., Clyde W. A., Jr Model systems for studying the pathogenesis of infections causing bronchiolitis in man. Pediatr Res. 1977 Mar;11(3 Pt 2):243–246. [PubMed] [Google Scholar]
  15. Däubener W., von Steldern D., Maxeiner B., Scheurich P., Pfizenmaier K. Postnatal development of functional T cell subsets in the mouse: a frequency analysis of mitogen reactive precursors of proliferating, of cytotoxic and of IL 2 producing T cells. Immunobiology. 1985 Jul;169(5):472–485. doi: 10.1016/S0171-2985(85)80003-6. [DOI] [PubMed] [Google Scholar]
  16. Glezen W. P. Reactive airway disorders in children. Role of respiratory virus infections. Clin Chest Med. 1984 Dec;5(4):635–643. [PubMed] [Google Scholar]
  17. Hall W. C., Ward J. M. A comparison of the avidin-biotin-peroxidase complex (ABC) and peroxidase-anti-peroxidase (PAP) immunocytochemical techniques for demonstrating Sendai virus infection in fixed tissue specimens. Lab Anim Sci. 1984 Jun;34(3):261–263. [PubMed] [Google Scholar]
  18. Hawthorne J. D., Albrecht P. Sensitive plaque neutralization assay for parainfluenza virus types 1, 2, and 3 and respiratory syncytial virus. J Clin Microbiol. 1981 Apr;13(4):730–737. doi: 10.1128/jcm.13.4.730-737.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Henderson F. W., Clyde W. A., Jr, Collier A. M., Denny F. W., Senior R. J., Sheaffer C. I., Conley W. G., 3rd, Christian R. M. The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice. J Pediatr. 1979 Aug;95(2):183–190. doi: 10.1016/s0022-3476(79)80647-2. [DOI] [PubMed] [Google Scholar]
  20. Jakab G. J., Warr G. A. Immune-enhanced phagocytic dysfunction in pulmonary macrophages infected with parainfluenza 1 (Sendai) virus. Am Rev Respir Dis. 1981 Nov;124(5):575–581. doi: 10.1164/arrd.1981.124.5.575. [DOI] [PubMed] [Google Scholar]
  21. Kattan M., Keens T. G., Lapierre J. G., Levison H., Bryan A. C., Reilly B. J. Pulmonary function abnormalities in symptom-free children after bronchiolitis. Pediatrics. 1977 May;59(5):683–688. [PubMed] [Google Scholar]
  22. Kauffman S. L., Burri P. H., Weibel E. R. The postnatal growth of the rat lung. II. Autoradiography. Anat Rec. 1974 Sep;180(1):63–76. doi: 10.1002/ar.1091800108. [DOI] [PubMed] [Google Scholar]
  23. McConnochie K. M., Roghmann K. J. Bronchiolitis as a possible cause of wheezing in childhood: new evidence. Pediatrics. 1984 Jul;74(1):1–10. [PubMed] [Google Scholar]
  24. McConnochie K. M., Roghmann K. J. Predicting clinically significant lower respiratory tract illness in childhood following mild bronchiolitis. Am J Dis Child. 1985 Jun;139(6):625–631. doi: 10.1001/archpedi.1985.02140080095042. [DOI] [PubMed] [Google Scholar]
  25. Mills J. Effects of Sendai virus infection on function of cultured mouse alveolar macrophages. Am Rev Respir Dis. 1979 Dec;120(6):1239–1244. doi: 10.1164/arrd.1979.120.6.1239. [DOI] [PubMed] [Google Scholar]
  26. Mintz L., Drew W. L., Hoo R., Finley T. N. Age-dependent resistance of human alveolar macrophages to herpes simplex virus. Infect Immun. 1980 May;28(2):417–420. doi: 10.1128/iai.28.2.417-420.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mok J. Y., Simpson H. Outcome for acute bronchitis, bronchiolitis, and pneumonia in infancy. Arch Dis Child. 1984 Apr;59(4):306–309. doi: 10.1136/adc.59.4.306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Parker J. C., O'Beirne A. J., Collins M. J., Jr Sensitivity of enzyme-linked immunosorbent assay, complement fixation, and hemagglutination inhibition serological tests for detection of Sendai virus antibody in laboratory mice. J Clin Microbiol. 1979 Mar;9(3):444–447. doi: 10.1128/jcm.9.3.444-447.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Prince G. A., Jenson A. B., Horswood R. L., Camargo E., Chanock R. M. The pathogenesis of respiratory syncytial virus infection in cotton rats. Am J Pathol. 1978 Dec;93(3):771–791. [PMC free article] [PubMed] [Google Scholar]
  30. Prince G. A., Porter D. D. The pathogenesis of respiratory syncytial virus infection in infant ferrets. Am J Pathol. 1976 Feb;82(2):339–352. [PMC free article] [PubMed] [Google Scholar]
  31. Reid L. Influence of the pattern of structural growth of lung on susceptibility to specific infectious diseases in infants and children. Pediatr Res. 1977 Mar;11(3 Pt 2):210–215. [PubMed] [Google Scholar]
  32. Riccardi C., Giampietri A., Migliorati G., Frati L., Herberman R. B. Studies on the mechanism of low natural killer cell activity in infant and aged mice. Nat Immun Cell Growth Regul. 1986;5(5):238–249. [PubMed] [Google Scholar]
  33. Robertson J. S., Naeve C. W., Webster R. G., Bootman J. S., Newman R., Schild G. C. Alterations in the hemagglutinin associated with adaptation of influenza B virus to growth in eggs. Virology. 1985 May;143(1):166–174. doi: 10.1016/0042-6822(85)90105-9. [DOI] [PubMed] [Google Scholar]
  34. Taylor G., Stott E. J., Hughes M., Collins A. P. Respiratory syncytial virus infection in mice. Infect Immun. 1984 Feb;43(2):649–655. doi: 10.1128/iai.43.2.649-655.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Unanue E. R., Allen P. M. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. doi: 10.1126/science.2437650. [DOI] [PubMed] [Google Scholar]
  36. Vidić B., Burri P. H. Morphometric analysis of the remodeling of the rat pulmonary epithelium during early postnatal development. Anat Rec. 1983 Oct;207(2):317–324. doi: 10.1002/ar.1092070210. [DOI] [PubMed] [Google Scholar]
  37. Wagener J. S., Minnich L., Sobonya R., Taussig L. M., Ray C. G., Fulginiti V. Parainfluenza type II infection in dogs. A model for viral lower respiratory tract infection in humans. Am Rev Respir Dis. 1983 Jun;127(6):771–775. doi: 10.1164/arrd.1983.127.6.771. [DOI] [PubMed] [Google Scholar]
  38. Ward J. M., Houchens D. P., Collins M. J., Young D. M., Reagan R. L. Naturally-occurring Sendai virus infection of athymic nude mice. Vet Pathol. 1976;13(1):36–46. doi: 10.1177/030098587601300105. [DOI] [PubMed] [Google Scholar]
  39. Wohl M. E., Chernick V. State of the art: bronchiolitis. Am Rev Respir Dis. 1978 Oct;118(4):759–781. doi: 10.1164/arrd.1978.118.4.759. [DOI] [PubMed] [Google Scholar]
  40. Zee Y. C., Osebold J. W., Dotson W. M. Antibody responses and interferon titers in the respiratory tracts of mice after aerosolized exposure to influenza virus. Infect Immun. 1979 Jul;25(1):202–207. doi: 10.1128/iai.25.1.202-207.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES