Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 Aug;137(2):385–392.

Epithelial cell-fibroblast interactions in lung injury and repair.

I Y Adamson 1, C Hedgecock 1, D H Bowden 1
PMCID: PMC1877605  PMID: 1696785

Abstract

Although direct intercellular contacts between alveolar epithelial cells and fibroblasts have been described in developing and adult lung, the frequency of such contacts and their relationship to type 2 cell division and differentiation in normal and abnormal repair is not known. The authors now correlate measurements of type 2 cell basal surface, basement membrane continuity, and the incidence of epithelial-interstitial cell contacts with the proliferative index of type 2 cells and fibroblasts in normal repair (after hyperoxia) and in abnormal repair with fibrosis (after bleomycin or butylated hydroxytoluene). In each case, type 1 cell necrosis was followed by an increase in type 2 cell basal surface as the cells spread over the denuded capillary wall before dividing. After hyperoxia, a high but short-lived peak in type 2 cell division was not accompanied by fibrosis. After more severe drug-induced injury, the type 2 proliferative phase was extended and was accompanied by prolonged fibroblast growth. Type 2 cells persisted where they covered a thick interstitium of fibroblasts and fibrillar collagen. The incidence of epithelial-interstitial cell contacts decreased at the time of maximal type 2 cell division, then increased immediately after the peak. The results suggest a reciprocal epithelial-fibroblast control system whereby 1) epithelial necrosis and delayed repair promotes fibroblast growth, and 2) direct contact of epithelial cells with fibroblasts or fibrillar collagen may provide a factor important for the regulation of type 2 cell growth and differentiation.

Full text

PDF
385

Images in this article

387Figure 1
on p.387
387Figure 2
on p.387
388Figure 5
on p.388
389Figure 6
on p.389
390Figure 8
on p.390
390Figure 9
on p.390

Selected References

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

  1. Adamson I. Y., Bowden D. H., Cote M. G., Witschi H. Lung injury induced by butylated hydroxytoluene: cytodynamic and biochemical studies in mice. Lab Invest. 1977 Jan;36(1):26–32. [PubMed] [Google Scholar]
  2. Adamson I. Y., Bowden D. H. Derivation of type 1 epithelium from type 2 cells in the developing rat lung. Lab Invest. 1975 Jun;32(6):736–745. [PubMed] [Google Scholar]
  3. Adamson I. Y., Bowden D. H. The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen. Lab Invest. 1974 Jan;30(1):35–42. [PubMed] [Google Scholar]
  4. Adamson I. Y. Drug-induced pulmonary fibrosis. Environ Health Perspect. 1984 Apr;55:25–36. doi: 10.1289/ehp.845525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Adamson I. Y., King G. M. Sex differences in development of fetal rat lung. II. Quantitative morphology of epithelial-mesenchymal interactions. Lab Invest. 1984 Apr;50(4):461–468. [PubMed] [Google Scholar]
  6. Adamson I. Y., Young L., Bowden D. H. Relationship of alveolar epithelial injury and repair to the induction of pulmonary fibrosis. Am J Pathol. 1988 Feb;130(2):377–383. [PMC free article] [PubMed] [Google Scholar]
  7. Bitterman P. B., Adelberg S., Crystal R. G. Mechanisms of pulmonary fibrosis. Spontaneous release of the alveolar macrophage-derived growth factor in the interstitial lung disorders. J Clin Invest. 1983 Nov;72(5):1801–1813. doi: 10.1172/JCI111140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brody A. R., Soler P., Basset F., Haschek W. M., Witschi H. Epithelial-mesenchymal associations of cells in human pulmonary fibrosis and in BHT-oxygen-induced fibrosis in mice. Exp Lung Res. 1981 Aug;2(3):207–220. doi: 10.3109/01902148109052316. [DOI] [PubMed] [Google Scholar]
  9. Chauncey J. B., Peters-Golden M., Simon R. H. Arachidonic acid metabolism by rat alveolar epithelial cells. Lab Invest. 1988 Feb;58(2):133–140. [PubMed] [Google Scholar]
  10. Elias J. A., Rossman M. D., Zurier R. B., Daniele R. P. Human alveolar macrophage inhibition of lung fibroblast growth. A prostaglandin-dependent process. Am Rev Respir Dis. 1985 Jan;131(1):94–99. doi: 10.1164/arrd.1985.131.1.94. [DOI] [PubMed] [Google Scholar]
  11. Geppert E. F., Williams M. C., Mason R. J. Primary culture of rat alveolar type II Cells on floating collagen membranes. Morphological and biochemical observations. Exp Cell Res. 1980 Aug;128(2):363–374. doi: 10.1016/0014-4827(80)90072-5. [DOI] [PubMed] [Google Scholar]
  12. Goldstein R. H., Polgar P. The effect and interaction of bradykinin and prostaglandins on protein and collagen production by lung fibroblasts. J Biol Chem. 1982 Aug 10;257(15):8630–8633. [PubMed] [Google Scholar]
  13. Haschek W. M., Witschi H. Pulmonary fibrosis--a possible mechanism. Toxicol Appl Pharmacol. 1979 Dec;51(3):475–487. doi: 10.1016/0041-008x(79)90372-7. [DOI] [PubMed] [Google Scholar]
  14. Lwebuga-Mukasa J. S., Thulin G., Madri J. A., Barrett C., Warshaw J. B. An acellular human amnionic membrane model for in vitro culture of type II pneumocytes: the role of the basement membrane in cell morphology and function. J Cell Physiol. 1984 Oct;121(1):215–225. doi: 10.1002/jcp.1041210127. [DOI] [PubMed] [Google Scholar]
  15. Madri J. A., Williams S. K. Capillary endothelial cell cultures: phenotypic modulation by matrix components. J Cell Biol. 1983 Jul;97(1):153–165. doi: 10.1083/jcb.97.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nash G., Blennerhassett J. B., Pontoppidan H. Pulmonary lesions associated with oxygen therapy and artifical ventilation. N Engl J Med. 1967 Feb 16;276(7):368–374. doi: 10.1056/NEJM196702162760702. [DOI] [PubMed] [Google Scholar]
  17. Smith B. T. Lung maturation in the fetal rat: acceleration by injection of fibroblast-pneumonocyte factor. Science. 1979 Jun 8;204(4397):1094–1095. doi: 10.1126/science.582216. [DOI] [PubMed] [Google Scholar]
  18. Smith B. T., Post M. Fibroblast-pneumonocyte factor. Am J Physiol. 1989 Oct;257(4 Pt 1):L174–L178. doi: 10.1152/ajplung.1989.257.4.L174. [DOI] [PubMed] [Google Scholar]
  19. Taylor L., Polgar P., McAteer J. A., Douglas W. H. Prostaglandin production by type II alveolar epithelial cells. Biochim Biophys Acta. 1979 Mar 29;572(3):502–509. doi: 10.1016/0005-2760(79)90157-7. [DOI] [PubMed] [Google Scholar]
  20. Terzaghi M., Nettesheim P., Williams M. L. Repopulation of denuded tracheal grafts with normal, preneoplastic, and neoplastic epithelial cell populations. Cancer Res. 1978 Dec;38(12):4546–4553. [PubMed] [Google Scholar]

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

RESOURCES