Skip to main content
NCBI home page
International Journal of Experimental Pathology logoLink to International Journal of Experimental Pathology
. 1995 Aug;76(4):287–298.

Alterations of surfactant lipid turnover in silicosis: evidence of a role for surfactant-associated protein A (SP-A).

O Lesur 1, T Bouhadiba 1, B Melloni 1, A Cantin 1, J A Whitsett 1, R Bégin 1
PMCID: PMC1997178  PMID: 7547443

Abstract

Type II cell hypertrophy with surfactant accumulation in the lung is a common observation in silicosis. Mechanisms leading to these alterations are poorly understood. By using silica dusts and alveolar fluids from saline and silica exposed sheep, we explored four different pathways of surfactant turnover in vitro: (1) synthesis and (2) secretion of lipids by rat type II cells; and dipalmitoylphosphatidylcholine (DPPC) uptake/reuptake by (3) type II cells and (4) alveolar macrophages. Silica had no direct specific effect on type II cell lipid metabolism. Alveolar fluids from both saline and silica exposed animals induced several alterations compared to control medium: (a) an increase in lipid synthesis (60 to 130%, P < 0.05); (b) a decrease in lipid secretion (25 to 70%, P < 0.05); (c) a 50 to 75% increase in DPPC reuptake by type II cells (P < 0.05); (d) a 65 to 75% decrease in DPPC uptake by alveolar macrophages (P < 0.05). DPPC uptake by in vivo silica exposed alveolar macrophages was reduced. Alterations of surfactant lipid metabolism induced by alveolar fluids from silicotic animals was more pronounced than in those treated with control fluids. Anti SP-A antibodies significantly suppressed most of the alveolar fluid induced effects on surfactant turnover. From these in vitro data, silica-induced type II cell hypertrophy seems to result from an increase in lipid synthesis activity and an imbalance in the lipid secretion/reuptake ratio.

Full text

PDF
287

Images in this article

291Figure 1
on p.291

Selected References

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

  1. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Bégin R., Cantin A., Massé S., Dufresne A., Perreault G., Sébastien P. Aluminium inhalation in sheep silicosis. Int J Exp Pathol. 1993 Jun;74(3):299–307. [PMC free article] [PubMed] [Google Scholar]
  4. Bégin R., Dufresne A., Cantin A., Possmayer F., Sébastien P., Fabi D., Bilodeau G., Martel M., Bisson D., Pietrowski B. Quartz exposure, retention, and early silicosis in sheep. Exp Lung Res. 1989 May;15(3):409–428. doi: 10.3109/01902148909087868. [DOI] [PubMed] [Google Scholar]
  5. Bégin R., Lesur O., Bouhadiba T., Guojian L., Larivée P., Melloni B., Martel M., Cantin A. Phospholipid content of bronchoalveolar lavage fluid in granite workers with silicosis in Quebec. Thorax. 1993 Aug;48(8):840–844. doi: 10.1136/thx.48.8.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bégin R., Possmayer F., Ormseth M. A., Martel M., Cantin A., Massé S. Effect of aluminum inhalation on alveolar phospholipid profiles in experimental silicosis. Lung. 1989;167(2):107–115. doi: 10.1007/BF02714937. [DOI] [PubMed] [Google Scholar]
  7. Cott G. R., Walker S. R., Mason R. J. The effect of substratum and serum on the lipid synthesis and morphology of alveolar type II cells in vitro. Exp Lung Res. 1987;13(4):427–447. doi: 10.3109/01902148709069603. [DOI] [PubMed] [Google Scholar]
  8. Dethloff L. A., Gilmore L. B., Brody A. R., Hook G. E. Induction of intra- and extra-cellular phospholipids in the lungs of rats exposed to silica. Biochem J. 1986 Jan 1;233(1):111–118. doi: 10.1042/bj2330111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dethloff L. A., Gladen B. C., Gilmore L. B., Hook G. E. Kinetics of pulmonary surfactant phosphatidylcholine metabolism in the lungs of silica-treated rats. Toxicol Appl Pharmacol. 1989 Mar 15;98(1):1–11. doi: 10.1016/0041-008x(89)90128-2. [DOI] [PubMed] [Google Scholar]
  10. Dobbs L. G., Wright J. R., Hawgood S., Gonzalez R., Venstrom K., Nellenbogen J. Pulmonary surfactant and its components inhibit secretion of phosphatidylcholine from cultured rat alveolar type II cells. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1010–1014. doi: 10.1073/pnas.84.4.1010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gonzalez-Rothi R. J., Harris J. O. Pulmonary alveolar proteinosis. Further evaluation of abnormal alveolar macrophages. Chest. 1986 Nov;90(5):656–661. doi: 10.1378/chest.90.5.656. [DOI] [PubMed] [Google Scholar]
  12. Hawgood S., Clements J. A. Pulmonary surfactant and its apoproteins. J Clin Invest. 1990 Jul;86(1):1–6. doi: 10.1172/JCI114670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heppleston A. G. Relationship of lipid secretion and particle size to diffuse interstitial change in pneumoconiosis: a pathogenetic perspective. Am J Ind Med. 1989;15(4):427–439. doi: 10.1002/ajim.4700150407. [DOI] [PubMed] [Google Scholar]
  14. Heppleston A. G. The role of surfactant in the pulmonary reaction to mineral particles. Int J Exp Pathol. 1991 Oct;72(5):599–616. [PMC free article] [PubMed] [Google Scholar]
  15. Heppleston A. G., Wright N. A., Stewart J. A. Experimental alveolar lipo-proteinosis following the inhalation of silica. J Pathol. 1970 Aug;101(4):293–307. doi: 10.1002/path.1711010402. [DOI] [PubMed] [Google Scholar]
  16. Kawada H., Horiuchi T., Shannon J. M., Kuroki Y., Voelker D. R., Mason R. J. Alveolar type II cells, surfactant protein A (SP-A), and the phospholipid components of surfactant in acute silicosis in the rat. Am Rev Respir Dis. 1989 Aug;140(2):460–470. doi: 10.1164/ajrccm/140.2.460. [DOI] [PubMed] [Google Scholar]
  17. Kuroki Y., Mason R. J., Voelker D. R. Alveolar type II cells express a high-affinity receptor for pulmonary surfactant protein A. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5566–5570. doi: 10.1073/pnas.85.15.5566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuroki Y., Mason R. J., Voelker D. R. Pulmonary surfactant apoprotein A structure and modulation of surfactant secretion by rat alveolar type II cells. J Biol Chem. 1988 Mar 5;263(7):3388–3394. [PubMed] [Google Scholar]
  19. Lesur O., Cantin A. M., Tanswell A. K., Melloni B., Beaulieu J. F., Bégin R. Silica exposure induces cytotoxicity and proliferative activity of type II pneumocytes. Exp Lung Res. 1992 Mar-Apr;18(2):173–190. doi: 10.3109/01902149209031679. [DOI] [PubMed] [Google Scholar]
  20. Lesur O., Melloni B., Cantin A. M., Bégin R. Silica-exposed lung fluids have a proliferative activity for type II epithelial cells: a study on human and sheep alveolar fluids. Exp Lung Res. 1992 Sep-Oct;18(5):633–654. doi: 10.3109/01902149209031699. [DOI] [PubMed] [Google Scholar]
  21. Lesur O., Veldhuizen R. A., Whitsett J. A., Hull W. M., Possmayer F., Cantin A., Bégin R. Surfactant-associated proteins (SP-A, SP-B) are increased proportionally to alveolar phospholipids in sheep silicosis. Lung. 1993;171(2):63–74. doi: 10.1007/BF00542334. [DOI] [PubMed] [Google Scholar]
  22. Miles P. R., Wright J. R., Bowman L., Castranova V. Incorporation of [3H]palmitate into disaturated phosphatidylcholines in alveolar type II cells isolated by centrifugal elutriation. Biochim Biophys Acta. 1983 Aug 29;753(1):107–118. doi: 10.1016/0005-2760(83)90104-2. [DOI] [PubMed] [Google Scholar]
  23. Miller B. E., Bakewell W. E., Katyal S. L., Singh G., Hook G. E. Induction of surfactant protein (SP-A) biosynthesis and SP-A mRNA in activated type II cells during acute silicosis in rats. Am J Respir Cell Mol Biol. 1990 Sep;3(3):217–226. doi: 10.1165/ajrcmb/3.3.217. [DOI] [PubMed] [Google Scholar]
  24. Miller B. E., Dethloff L. A., Gladen B. C., Hook G. E. Progression of type II cell hypertrophy and hyperplasia during silica-induced pulmonary inflammation. Lab Invest. 1987 Nov;57(5):546–554. [PubMed] [Google Scholar]
  25. Miller B. E., HooK G. E. Regulation of phosphatidylcholine biosynthesis in activated alveolar type II cells. Am J Respir Cell Mol Biol. 1989 Aug;1(2):127–136. doi: 10.1165/ajrcmb/1.2.127. [DOI] [PubMed] [Google Scholar]
  26. Miller B. E., Hook G. E. Isolation and characterization of hypertrophic type II cells from the lungs of silica-treated rats. Lab Invest. 1988 May;58(5):565–575. [PubMed] [Google Scholar]
  27. Panos R. J., Suwabe A., Leslie C. C., Mason R. J. Hypertrophic alveolar type II cells from silica-treated rats are committed to DNA synthesis in vitro. Am J Respir Cell Mol Biol. 1990 Jul;3(1):51–59. doi: 10.1165/ajrcmb/3.1.51. [DOI] [PubMed] [Google Scholar]
  28. Rami J., Sasic S. M., Rooney S. A. Enhanced fatty acid biosynthesis and normal surfactant secretion in hypertrophic rat type II cells. Am J Physiol. 1991 Jun;260(6 Pt 1):L577–L585. doi: 10.1152/ajplung.1991.260.6.L577. [DOI] [PubMed] [Google Scholar]
  29. Rice W. R., Ross G. F., Singleton F. M., Dingle S., Whitsett J. A. Surfactant-associated protein inhibits phospholipid secretion from type II cells. J Appl Physiol (1985) 1987 Aug;63(2):692–698. doi: 10.1152/jappl.1987.63.2.692. [DOI] [PubMed] [Google Scholar]
  30. Rider E. D., Ikegami M., Jobe A. H. Localization of alveolar surfactant clearance in rabbit lung cells. Am J Physiol. 1992 Aug;263(2 Pt 1):L201–L209. doi: 10.1152/ajplung.1992.263.2.L201. [DOI] [PubMed] [Google Scholar]
  31. Rooney S. A. The surfactant system and lung phospholipid biochemistry. Am Rev Respir Dis. 1985 Mar;131(3):439–460. doi: 10.1164/arrd.1985.131.3.439. [DOI] [PubMed] [Google Scholar]
  32. Ryan R. M., Morris R. E., Rice W. R., Ciraolo G., Whitsett J. A. Binding and uptake of pulmonary surfactant protein (SP-A) by pulmonary type II epithelial cells. J Histochem Cytochem. 1989 Apr;37(4):429–440. doi: 10.1177/37.4.2926121. [DOI] [PubMed] [Google Scholar]
  33. Suwabe A., Panos R. J., Voelker D. R. Alveolar type II cells isolated after silica-induced lung injury in rats have increased surfactant protein A (SP-A) receptor activity. Am J Respir Cell Mol Biol. 1991 Mar;4(3):264–272. doi: 10.1165/ajrcmb/4.3.264. [DOI] [PubMed] [Google Scholar]
  34. Thakur N. R., Tesan M., Tyler N. E., Bleasdale J. E. Altered lipid synthesis in type II pneumonocytes exposed to lung surfactant. Biochem J. 1986 Dec 15;240(3):679–690. doi: 10.1042/bj2400679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wright J. R., Dobbs L. G. Regulation of pulmonary surfactant secretion and clearance. Annu Rev Physiol. 1991;53:395–414. doi: 10.1146/annurev.ph.53.030191.002143. [DOI] [PubMed] [Google Scholar]
  36. Wright J. R., Wager R. E., Hawgood S., Dobbs L., Clements J. A. Surfactant apoprotein Mr = 26,000-36,000 enhances uptake of liposomes by type II cells. J Biol Chem. 1987 Feb 25;262(6):2888–2894. [PubMed] [Google Scholar]

Articles from International Journal of Experimental Pathology are provided here courtesy of Wiley

RESOURCES