Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Jun;93(6):2608–2615. doi: 10.1172/JCI117273

Exposure of the hydrophobic components of porcine lung surfactant to oxidant stress alters surface tension properties.

N Gilliard 1, G P Heldt 1, J Loredo 1, H Gasser 1, H Redl 1, T A Merritt 1, R G Spragg 1
PMCID: PMC294496  PMID: 8200999

Abstract

We have tested the hypothesis that oxidation of lung surfactant results in loss of surface tension lowering function. Porcine lung surfactant was exposed to conditions known to cause lipid peroxidation (0.2 mM FeCl2 + 0.1 mM H2O2 or 5 microM CuCl2). Lipid peroxidation was verified by detection of conjugated dienes, thiobarbituric acid reactive substances, fluorescent products, hydroxy alkenals, and loss of unsaturated fatty acids. Exposed samples had significantly diminished surface tension lowering ability in vitro as measured in a bubble surfactometer. Samples exposed to FeCl2 + H2O2 had significantly diminished surface tension lowering ability in vivo as indicated by their reduced ability to improve lung compliance of surfactant-deficient fetal rabbits. Oxidation of phospholipid mixtures with surface tension lowering activity and containing unsaturated acyl groups resulted in partial loss of activity as determined in vitro. These results suggest that the effect of oxidants on lung surfactant function is due, in part, to effects on the phospholipid components and that acute pulmonary inflammation accompanied by oxygen radical production may result in surfactant lipid peroxidation and loss of surface tension lowering function.

Full text

PDF
2610

Selected References

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

  1. Ashbaugh D. G., Bigelow D. B., Petty T. L., Levine B. E. Acute respiratory distress in adults. Lancet. 1967 Aug 12;2(7511):319–323. doi: 10.1016/s0140-6736(67)90168-7. [DOI] [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. Bachofen M., Weibel E. R. Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis. 1977 Oct;116(4):589–615. doi: 10.1164/arrd.1977.116.4.589. [DOI] [PubMed] [Google Scholar]
  4. Baldwin S. R., Simon R. H., Grum C. M., Ketai L. H., Boxer L. A., Devall L. J. Oxidant activity in expired breath of patients with adult respiratory distress syndrome. Lancet. 1986 Jan 4;1(8471):11–14. doi: 10.1016/s0140-6736(86)91895-7. [DOI] [PubMed] [Google Scholar]
  5. Berggren P., Lachmann B., Curstedt T., Grossmann G., Robertson B. Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage. Acta Anaesthesiol Scand. 1986 May;30(4):321–328. doi: 10.1111/j.1399-6576.1986.tb02423.x. [DOI] [PubMed] [Google Scholar]
  6. Biesalski H., Greiff H., Brodda K., Hafner G., Bässler K. H. Rapid determination of vitamin A (retinol) and vitamin E (alpha-tocopherol) in human serum by isocratic adsorption HPLC. Int J Vitam Nutr Res. 1986;56(4):319–327. [PubMed] [Google Scholar]
  7. Cantin A. M., Fells G. A., Hubbard R. C., Crystal R. G. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract. J Clin Invest. 1990 Sep;86(3):962–971. doi: 10.1172/JCI114798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cochrane C. G., Spragg R. G., Revak S. D., Cohen A. B., McGuire W. W. The presence of neutrophil elastase and evidence of oxidation activity in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome. Am Rev Respir Dis. 1983 Feb;127(2):S25–S27. doi: 10.1164/arrd.1983.127.2P2.S25. [DOI] [PubMed] [Google Scholar]
  9. DAHLE L. K., HILL E. G., HOLMAN R. T. The thiobarbituric acid reaction and the autoxidations of polyunsaturated fatty acid methyl esters. Arch Biochem Biophys. 1962 Aug;98:253–261. doi: 10.1016/0003-9861(62)90181-9. [DOI] [PubMed] [Google Scholar]
  10. Engstrom P. C., Holm B. A., Matalon S. Surfactant replacement attenuates the increase in alveolar permeability in hyperoxia. J Appl Physiol (1985) 1989 Aug;67(2):688–693. doi: 10.1152/jappl.1989.67.2.688. [DOI] [PubMed] [Google Scholar]
  11. Enhorning G. Pulsating bubble technique for evaluating pulmonary surfactant. J Appl Physiol Respir Environ Exerc Physiol. 1977 Aug;43(2):198–203. doi: 10.1152/jappl.1977.43.2.198. [DOI] [PubMed] [Google Scholar]
  12. Esterbauer H., Cheeseman K. H., Dianzani M. U., Poli G., Slater T. F. Separation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2+ in rat liver microsomes. Biochem J. 1982 Oct 15;208(1):129–140. doi: 10.1042/bj2080129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Esterbauer H., Striegl G., Puhl H., Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun. 1989;6(1):67–75. doi: 10.3109/10715768909073429. [DOI] [PubMed] [Google Scholar]
  14. Fujiwara T., Maeta H., Chida S., Morita T., Watabe Y., Abe T. Artificial surfactant therapy in hyaline-membrane disease. Lancet. 1980 Jan 12;1(8159):55–59. doi: 10.1016/s0140-6736(80)90489-4. [DOI] [PubMed] [Google Scholar]
  15. Gregory T. J., Longmore W. J., Moxley M. A., Whitsett J. A., Reed C. R., Fowler A. A., 3rd, Hudson L. D., Maunder R. J., Crim C., Hyers T. M. Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. J Clin Invest. 1991 Dec;88(6):1976–1981. doi: 10.1172/JCI115523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gutteridge J. M. Thiobarbituric acid-reactivity following iron-dependent free-radical damage to amino acids and carbohydrates. FEBS Lett. 1981 Jun 15;128(2):343–346. doi: 10.1016/0014-5793(81)80113-5. [DOI] [PubMed] [Google Scholar]
  17. Hallman M., Spragg R., Harrell J. H., Moser K. M., Gluck L. Evidence of lung surfactant abnormality in respiratory failure. Study of bronchoalveolar lavage phospholipids, surface activity, phospholipase activity, and plasma myoinositol. J Clin Invest. 1982 Sep;70(3):673–683. doi: 10.1172/JCI110662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Holm B. A., Keicher L., Liu M. Y., Sokolowski J., Enhorning G. Inhibition of pulmonary surfactant function by phospholipases. J Appl Physiol (1985) 1991 Jul;71(1):317–321. doi: 10.1152/jappl.1991.71.1.317. [DOI] [PubMed] [Google Scholar]
  19. Holm B. A., Notter R. H., Siegle J., Matalon S. Pulmonary physiological and surfactant changes during injury and recovery from hyperoxia. J Appl Physiol (1985) 1985 Nov;59(5):1402–1409. doi: 10.1152/jappl.1985.59.5.1402. [DOI] [PubMed] [Google Scholar]
  20. Kendig J. W., Notter R. H., Cox C., Aschner J. L., Benn S., Bernstein R. M., Hendricks-Munoz K., Maniscalco W. M., Metlay L. A., Phelps D. L. Surfactant replacement therapy at birth: final analysis of a clinical trial and comparisons with similar trials. Pediatrics. 1988 Nov;82(5):756–762. [PubMed] [Google Scholar]
  21. King R. J. Pulmonary surfactant. J Appl Physiol Respir Environ Exerc Physiol. 1982 Jul;53(1):1–8. doi: 10.1152/jappl.1982.53.1.1. [DOI] [PubMed] [Google Scholar]
  22. Lachmann B. Animal models and clinical pilot studies of surfactant replacement in adult respiratory distress syndrome. Eur Respir J Suppl. 1989 Mar;3:98s–103s. [PubMed] [Google Scholar]
  23. Lee C. T., Fein A. M., Lippmann M., Holtzman H., Kimbel P., Weinbaum G. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome. N Engl J Med. 1981 Jan 22;304(4):192–196. doi: 10.1056/NEJM198101223040402. [DOI] [PubMed] [Google Scholar]
  24. Liau D. F., Barrett C. R., Bell A. L., Ryan S. F. Functional abnormalities of lung surfactant in experimental acute alveolar injury in the dog. Am Rev Respir Dis. 1987 Aug;136(2):395–401. doi: 10.1164/ajrccm/136.2.395. [DOI] [PubMed] [Google Scholar]
  25. Lunec J., Halloran S. P., White A. G., Dormandy T. L. Free-radical oxidation (peroxidation) products in serum and synovial fluid in rheumatoid arthritis. J Rheumatol. 1981 Mar-Apr;8(2):233–245. [PubMed] [Google Scholar]
  26. McGuire W. W., Spragg R. G., Cohen A. B., Cochrane C. G. Studies on the pathogenesis of the adult respiratory distress syndrome. J Clin Invest. 1982 Mar;69(3):543–553. doi: 10.1172/JCI110480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Minotti G., Aust S. D. The requirement for iron (III) in the initiation of lipid peroxidation by iron (II) and hydrogen peroxide. J Biol Chem. 1987 Jan 25;262(3):1098–1104. [PubMed] [Google Scholar]
  28. Mohsenin V. Lipid peroxidation and antielastase activity in the lung under oxidant stress: role of antioxidant defenses. J Appl Physiol (1985) 1991 Apr;70(4):1456–1462. doi: 10.1152/jappl.1991.70.4.1456. [DOI] [PubMed] [Google Scholar]
  29. Palinski W., Ylä-Herttuala S., Rosenfeld M. E., Butler S. W., Socher S. A., Parthasarathy S., Curtiss L. K., Witztum J. L. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis. 1990 May-Jun;10(3):325–335. doi: 10.1161/01.atv.10.3.325. [DOI] [PubMed] [Google Scholar]
  30. Pison U., Seeger W., Buchhorn R., Joka T., Brand M., Obertacke U., Neuhof H., Schmit-Neuerburg K. P. Surfactant abnormalities in patients with respiratory failure after multiple trauma. Am Rev Respir Dis. 1989 Oct;140(4):1033–1039. doi: 10.1164/ajrccm/140.4.1033. [DOI] [PubMed] [Google Scholar]
  31. Richman P. S., Spragg R. G., Robertson B., Merritt T. A., Curstedt T. The adult respiratory distress syndrome: first trials with surfactant replacement. Eur Respir J Suppl. 1989 Mar;3:109s–111s. [PubMed] [Google Scholar]
  32. Robertson B. European multicenter trials of curosurf for treatment of neonatal respiratory distress syndrome. Lung. 1990;168 (Suppl):860–863. doi: 10.1007/BF02718220. [DOI] [PubMed] [Google Scholar]
  33. Rouser G., Fkeischer S., Yamamoto A. Two dimensional then layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids. 1970 May;5(5):494–496. doi: 10.1007/BF02531316. [DOI] [PubMed] [Google Scholar]
  34. Ryan S. F., Ghassibi Y., Liau D. F. Effects of activated polymorphonuclear leukocytes upon pulmonary surfactant in vitro. Am J Respir Cell Mol Biol. 1991 Jan;4(1):33–41. doi: 10.1165/ajrcmb/4.1.33. [DOI] [PubMed] [Google Scholar]
  35. Schlag G., Voigt W. H., Schnells G., Glatzl A. Vergleichende Untersuchungen der Ultrastruktur von menschlicher Lunge und Skeletmuskulatur im Schock. II. Anaesthesist. 1977 Nov;26(11):612–622. [PubMed] [Google Scholar]
  36. Sedlak J., Lindsay R. H. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968 Oct 24;25(1):192–205. doi: 10.1016/0003-2697(68)90092-4. [DOI] [PubMed] [Google Scholar]
  37. Seeger W., Lepper H., Wolf H. R., Neuhof H. Alteration of alveolar surfactant function after exposure to oxidative stress and to oxygenated and native arachidonic acid in vitro. Biochim Biophys Acta. 1985 Jun 14;835(1):58–67. doi: 10.1016/0005-2760(85)90030-x. [DOI] [PubMed] [Google Scholar]
  38. Spragg R. G., Gilliard N., Richman P., Smith R. M., Hite R. D., Pappert D., Robertson B., Curstedt T., Strayer D. Acute effects of a single dose of porcine surfactant on patients with the adult respiratory distress syndrome. Chest. 1994 Jan;105(1):195–202. doi: 10.1378/chest.105.1.195. [DOI] [PubMed] [Google Scholar]
  39. Steinbrecher U. P., Parthasarathy S., Leake D. S., Witztum J. L., Steinberg D. Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3883–3887. doi: 10.1073/pnas.81.12.3883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ward P. A., Till G. O., Hatherill J. R., Annesley T. M., Kunkel R. G. Systemic complement activation, lung injury, and products of lipid peroxidation. J Clin Invest. 1985 Aug;76(2):517–527. doi: 10.1172/JCI112001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Weiss S. J. Tissue destruction by neutrophils. N Engl J Med. 1989 Feb 9;320(6):365–376. doi: 10.1056/NEJM198902093200606. [DOI] [PubMed] [Google Scholar]
  42. Wewers M. D., Herzyk D. J., Gadek J. E. Alveolar fluid neutrophil elastase activity in the adult respiratory distress syndrome is complexed to alpha-2-macroglobulin. J Clin Invest. 1988 Oct;82(4):1260–1267. doi: 10.1172/JCI113724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Yu S., Harding P. G., Smith N., Possmayer F. Bovine pulmonary surfactant: chemical composition and physical properties. Lipids. 1983 Aug;18(8):522–529. doi: 10.1007/BF02535391. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES