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Modification of surfactant metabolizing cells in rat lung by clofibrate, a hypolipidemic peroxisome proliferating agent

Evidence to suggest that clofibrate influences pulmonary surfactant metabolism

Virchows Archiv B volume 54, pages 232–240 (1987)Cite this article

Summary

The influence of clofibrate (ethyl-α-pchlorophenoxy-isobutyrate), a hypolipidemic peroxisome proliferating agent, has been tested on the lungs of adult male rats. Drug administration for 7 days caused structural changes in two types of lung cells, both of which are involved in the metabolism of the pulmonary surfactant. By light microscopy the prominent features were the presence of enlarged type II alveolar epithelial cells and foamy intraalveolar macrophages. Compared with controls, type II cells in treated rats apparently contained more numerous surfactant-containing lamellar bodies, as visualized in semi-thin sections of Epon-embedded tissue. This difference was quantified morphometrically by light microscopy: the number of lamellar bodies was estimated as the profile number per individual type II alveolar cell, transsected at its nucleus. Clofibrate administration for 7 days resulted in a significant increase in the number of the lamellar inclusions. In contrast the number of type II alveolar cells per area of lung remained unchanged. There was no evidence of atelectasis or inflammatory infiltration in the drug-treated lungs, a finding confirmed in sections of perfusion-fixed, paraffin-embedded whole lung-lobes. By electron microscopy the lamellar inclusion bodies in the type II alveolar cells in treated rats, apart from being more numerous and sometimes smaller, were morphologically identical to those in controls. The vacuolated alveolar macrophages seen in treated rats also contained various lamellar phospholipid inclusions. Some of the alveoli in the treated animals showed a slightly increased acellular lining layer consisting of membranous bodies and lattices of tubular surfactant myelin. The data obtained support the view that clofibrate enhances the amount of intracellular pulmonary surfactant, although it is unclear if this results from an increase in the rate of surfactant synthesis or a decrease in the rate of surfactant secretion. Since clofibrate is known to increase the number of lipid metabolizing peroxisomes in rodent hepatocytes, it well be of interest in future studies to determine whether the changes observed in surfactant-metabolizing lung cells will be associated with the proliferation of pulmonary peroxisomes.

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Affiliations

  1. Institute of Pathology, Ludwig-Aschoff-Haus, University of Freiburg, FRG

    Birgitta Fringes, Karin Gorgas & Albrecht Reith

  2. Institute of Pathology, University of Freiburg, Albertstraße 19, D-7800, Freiburg

    Birgitta Fringes

  3. Department of Anatomy II, University of Heidelberg, D-6900, Heidelberg

    Karin Gorgas

  4. The Norwegian Radiumhospital and Institute for Cancer Research, N-Oslo-3, Norway

    Albrecht Reith

Authors
  1. Birgitta Fringes
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  2. Karin Gorgas
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  3. Albrecht Reith
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Fringes, B., Gorgas, K. & Reith, A. Modification of surfactant metabolizing cells in rat lung by clofibrate, a hypolipidemic peroxisome proliferating agent. Virchows Archiv B Cell Pathol 54, 232–240 (1987). https://doi.org/10.1007/BF02899216

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  • DOI: https://doi.org/10.1007/BF02899216

Key words

  • Clofibrate
  • Lung
  • Type II alveolar cells
  • Surfactant
  • Alveolar macrophages, perotisomes