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. 1986 Mar;77(3):789–796. doi: 10.1172/JCI112376

Deficiency of vitamin E in the alveolar fluid of cigarette smokers. Influence on alveolar macrophage cytotoxicity.

E R Pacht, H Kaseki, J R Mohammed, D G Cornwell, W B Davis
PMCID: PMC423465  PMID: 3949977

Abstract

Cigarette smoking produces oxidant-mediated changes in the lung important to the pathogenesis of emphysema. Since vitamin E can neutralize reactive oxygen species and prevent peroxidation of unsaturated lipids, it may constitute an important component of the lung's defense against oxidant injury. To better characterize the antioxidant protective role of vitamin E, young asymptomatic smokers and nonsmokers were evaluated by bronchoalveolar lavage before and immediately after a 3-wk course of oral vitamin E (2,400 IU/d). Smoker alveolar fluid at baseline was relatively deficient in vitamin E compared with nonsmoker fluid (3.1 +/- 0.7 ng/ml vs. 20.7 +/- 2.4 ng/ml, P less than 0.005). Although smoker alveolar fluid vitamin E levels increased to 9.3 +/- 2.3 ng/ml after supplementation, the levels remained significantly lower than nonsmoker baseline levels (P less than 0.01). This deficiency was explained, in part, by the increased oxidative metabolism of vitamin E to the quinone form in the lungs of smokers compared with nonsmokers. Although the significance of a lower concentration of alveolar fluid vitamin E is unclear, it may compromise the antioxidant protection afforded by the alveolar fluid as it coats the lung's epithelial surface. The protective role of vitamin E was assessed by cytotoxicity experiments, which demonstrated that the killing of normal rat lung parenchymal cells by smoker alveolar macrophages was inversely related to the vitamin E content of the parenchymal cells. These findings suggest that vitamin E may be an important lower respiratory tract antioxidant, and that the deficiency seen in young smokers may predispose them to an enhanced oxidant attack on their lung parenchymal cells.

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Selected References

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  1. Babior B. M., Kipnes R. S., Curnutte J. T. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744. doi: 10.1172/JCI107236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Babior B. M. Oxygen-dependent microbial killing by phagocytes (second of two parts). N Engl J Med. 1978 Mar 30;298(13):721–725. doi: 10.1056/NEJM197803302981305. [DOI] [PubMed] [Google Scholar]
  3. Baehner R. L., Boxer L. A., Ingraham L. M., Butterick C., Haak R. A. The influence of vitamin E on human polymorphonuclear cell metabolism and function. Ann N Y Acad Sci. 1982;393:237–250. doi: 10.1111/j.1749-6632.1982.tb31265.x. [DOI] [PubMed] [Google Scholar]
  4. Bell D. Y., Haseman J. A., Spock A., McLennan G., Hook G. E. Plasma proteins of the bronchoalveolar surface of the lungs of smokers and nonsmokers. Am Rev Respir Dis. 1981 Jul;124(1):72–79. doi: 10.1164/arrd.1981.124.1.72. [DOI] [PubMed] [Google Scholar]
  5. Bieri J. G., Corash L., Hubbard V. S. Medical uses of vitamin E. N Engl J Med. 1983 May 5;308(18):1063–1071. doi: 10.1056/NEJM198305053081805. [DOI] [PubMed] [Google Scholar]
  6. Block E. R. Potentiation of acute paraquat toxicity by vitamin E deficiency. Lung. 1979;156(3):195–203. doi: 10.1007/BF02714010. [DOI] [PubMed] [Google Scholar]
  7. Boyd M. R., Catignani G. L., Sasame H. A., Mitchell J. R., Stiko A. W. Acute pulmonary injury in rats by nitrofurantoin and modification by vitamin E, dietary fat, and oxygen. Am Rev Respir Dis. 1979 Jul;120(1):93–99. doi: 10.1164/arrd.1979.120.1.93. [DOI] [PubMed] [Google Scholar]
  8. Bucher J. R., Roberts R. J. Effects of alpha-tocopherol treatment on newborn rat lung development and injury in hyperoxia. Pediatr Pharmacol (New York) 1982;2(1):1–9. [PubMed] [Google Scholar]
  9. Buttriss J. L., Diplock A. T. High-performance liquid chromatography methods for vitamin E in tissues. Methods Enzymol. 1984;105:131–138. doi: 10.1016/s0076-6879(84)05018-7. [DOI] [PubMed] [Google Scholar]
  10. Carp H., Janoff A. Potential mediator of inflammation. Phagocyte-derived oxidants suppress the elastase-inhibitory capacity of alpha 1-proteinase inhibitor in vitro. J Clin Invest. 1980 Nov;66(5):987–995. doi: 10.1172/JCI109968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Carp H., Miller F., Hoidal J. R., Janoff A. Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2041–2045. doi: 10.1073/pnas.79.6.2041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chow C. K., Chen L. H., Thacker R. R., Griffith R. B. Dietary vitamin E and pulmonary biochemical responses of rats to cigarette smoking. Environ Res. 1984 Jun;34(1):8–17. doi: 10.1016/0013-9351(84)90070-7. [DOI] [PubMed] [Google Scholar]
  13. Chow C. K., Tappel A. L. An enzymatic protective mechanism against lipid peroxidation damage to lungs of ozone-exposed rats. Lipids. 1972 Aug;7(8):518–524. doi: 10.1007/BF02533017. [DOI] [PubMed] [Google Scholar]
  14. Cohen A. B., James H. L. Reduction of the elastase inhibitory capacity of alpha 1-antitrypsin by peroxides in cigarette smoke: an analysis of brands and filters. Am Rev Respir Dis. 1982 Jul;126(1):25–30. doi: 10.1164/arrd.1982.126.1.25. [DOI] [PubMed] [Google Scholar]
  15. Combs G. F., Jr, Noguchi T., Scott M. L. Mechanisms of action of selenium and vitamin E in protection of biological membranes. Fed Proc. 1975 Oct;34(11):2090–2095. [PubMed] [Google Scholar]
  16. Corash L., Spielberg S., Bartsocas C., Boxer L., Steinherz R., Sheetz M., Egan M., Schlessleman J., Schulman J. D. Reduced chronic hemolysis during high-dose vitamin E administration in Mediterranean-type glucose-6-phosphate dehydrogenase deficiency. N Engl J Med. 1980 Aug 21;303(8):416–420. doi: 10.1056/NEJM198008213030802. [DOI] [PubMed] [Google Scholar]
  17. DRAPER H. H., BERGAN J. G., CHIU M., CSALLANY A. S., BOARO A. V. A FURTHER STUDY OF THE SPECIFICITY OF THE VITAMIN E REQUIREMENT FOR REPRODUCTION. J Nutr. 1964 Dec;84:395–400. doi: 10.1093/jn/84.4.395. [DOI] [PubMed] [Google Scholar]
  18. Elsayed N. M., Mustafa M. G. Dietary antioxidants and the biochemical response to oxidant inhalation. I. Influence of dietary vitamin E on the biochemical effects of nitrogen dioxide exposure in rat lung. Toxicol Appl Pharmacol. 1982 Dec;66(3):319–328. doi: 10.1016/0041-008x(82)90298-8. [DOI] [PubMed] [Google Scholar]
  19. Fletcher B. L., Tappel A. L. Protective effects of dietary -tocopherol in rats exposed to toxic levels of ozone and nitrogen dioxide. Environ Res. 1973 Jun;6(2):165–175. doi: 10.1016/0013-9351(73)90030-3. [DOI] [PubMed] [Google Scholar]
  20. Gadek J. E., Fells G. A., Crystal R. G. Cigarette smoking induces functional antiprotease deficiency in the lower respiratory tract of humans. Science. 1979 Dec 14;206(4424):1315–1316. doi: 10.1126/science.316188. [DOI] [PubMed] [Google Scholar]
  21. Gadek J. E., Fells G. A., Zimmerman R. L., Rennard S. I., Crystal R. G. Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema. J Clin Invest. 1981 Oct;68(4):889–898. doi: 10.1172/JCI110344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gairola C., Matulionis D. H., Reasor M. J. Chlorphentermine-induced alterations in the lungs of vitamin E-deficient and supplemented rats: 1. Biochemical and morphometric analysis of the pulmonary response. Exp Mol Pathol. 1983 Jun;38(3):368–379. doi: 10.1016/0014-4800(83)90076-x. [DOI] [PubMed] [Google Scholar]
  23. Galdston M., Levytska V., Schwartz M. S., Magnússon B. Ceruloplasmin. Increased serum concentration and impaired antioxidant activity in cigarette smokers, and ability to prevent suppression of elastase inhibitory capacity of alpha 1-proteinase inhibitor. Am Rev Respir Dis. 1984 Feb;129(2):258–263. [PubMed] [Google Scholar]
  24. Gavino V. C., Miller J. S., Ikharebha S. O., Milo G. E., Cornwell D. G. Effect of polyunsaturated fatty acids and antioxidants on lipid peroxidation in tissue cultures. J Lipid Res. 1981 Jul;22(5):763–769. [PubMed] [Google Scholar]
  25. HAAGEN-SMIT A. J., BRUNELLE M. F., HARA J. Nitrogen oxide content of smokes from different types of tobacco. AMA Arch Ind Health. 1959 Nov;20:399–400. [PubMed] [Google Scholar]
  26. Hatam L. J., Kayden H. J. A high-performance liquid chromatographic method for the determination of tocopherol in plasma and cellular elements of the blood. J Lipid Res. 1979 Jul;20(5):639–645. [PubMed] [Google Scholar]
  27. Hittner H. M., Godio L. B., Rudolph A. J., Adams J. M., Garcia-Prats J. A., Friedman Z., Kautz J. A., Monaco W. A. Retrolental fibroplasia: efficacy of vitamin E in a double-blind clinical study of preterm infants. N Engl J Med. 1981 Dec 3;305(23):1365–1371. doi: 10.1056/NEJM198112033052301. [DOI] [PubMed] [Google Scholar]
  28. Hoidal J. R., Fox R. B., LeMarbe P. A., Perri R., Repine J. E. Altered oxidative metabolic responses in vitro of alveolar macrophages from asymptomatic cigarette smokers. Am Rev Respir Dis. 1981 Jan;123(1):85–89. doi: 10.1164/arrd.1981.123.1.85. [DOI] [PubMed] [Google Scholar]
  29. Hunninghake G. W., Crystal R. G. Cigarette smoking and lung destruction. Accumulation of neutrophils in the lungs of cigarette smokers. Am Rev Respir Dis. 1983 Nov;128(5):833–838. doi: 10.1164/arrd.1983.128.5.833. [DOI] [PubMed] [Google Scholar]
  30. Hunninghake G. W., Gadek J. E., Kawanami O., Ferrans V. J., Crystal R. G. Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage. Am J Pathol. 1979 Oct;97(1):149–206. [PMC free article] [PubMed] [Google Scholar]
  31. Janoff A., Carp H., Laurent P., Raju L. The role of oxidative processes in emphysema. Am Rev Respir Dis. 1983 Feb;127(2):S31–S38. doi: 10.1164/arrd.1983.127.2P2.S31. [DOI] [PubMed] [Google Scholar]
  32. Kornbrust D. J., Mavis R. D. Relative susceptibility of microsomes from lung, heart, liver, kidney, brain and testes to lipid peroxidation: correlation with vitamin E content. Lipids. 1980 May;15(5):315–322. doi: 10.1007/BF02533546. [DOI] [PubMed] [Google Scholar]
  33. Lentz P. E., Di Luzio N. R. Peroxidation of lipids in alveolar macrophages. Production by aqueous extracts of cigarette smoke. Arch Environ Health. 1974 May;28(5):279–282. doi: 10.1080/00039896.1974.10666487. [DOI] [PubMed] [Google Scholar]
  34. Lindsey J. A., Zhang H. F., Kaseki H., Morisaki N., Sato T., Cornwell D. G. Fatty acid metabolism and cell proliferation. VII. Antioxidant effects of tocopherols and their quinones. Lipids. 1985 Mar;20(3):151–157. doi: 10.1007/BF02534247. [DOI] [PubMed] [Google Scholar]
  35. MARGOLIASH E., FROHWIRT N. Spectrum of horse-heart cytochrome c. Biochem J. 1959 Mar;71(3):570–572. doi: 10.1042/bj0710570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Machlin L. J., Gabriel E. Kinetics of tissue alpha-tocopherol uptake and depletion following administration of high levels of vitamin E. Ann N Y Acad Sci. 1982;393:48–60. doi: 10.1111/j.1749-6632.1982.tb31231.x. [DOI] [PubMed] [Google Scholar]
  37. Martin W. J., 2nd, Gadek J. E., Hunninghake G. W., Crystal R. G. Oxidant injury of lung parenchymal cells. J Clin Invest. 1981 Nov;68(5):1277–1288. doi: 10.1172/JCI110374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. McGowan S. E., Parenti C. M., Hoidal J. R., Niewoehner D. E. Ascorbic acid content and accumulation by alveolar macrophages from cigarette smokers and nonsmokers. J Lab Clin Med. 1984 Jul;104(1):127–134. [PubMed] [Google Scholar]
  39. Morisaki N., Lindsey J. A., Stitts J. M., Zhang H., Cornwell D. G. Fatty acid metabolism and cell proliferation. V. Evaluation of pathways for the generation of lipid peroxides. Lipids. 1984 Jun;19(6):381–394. doi: 10.1007/BF02537399. [DOI] [PubMed] [Google Scholar]
  40. Roehm J. N., Hadley J. G., Menzel D. B. The influence of vitamin E on the lung fatty acids of rats exposed to ozone. Arch Environ Health. 1972 Apr;24(4):237–242. doi: 10.1080/00039896.1972.10666077. [DOI] [PubMed] [Google Scholar]
  41. Sato S., Kawakami M., Maeda S., Takishima T. Scanning electron microscopy of the lungs of vitamin E-deficient rats exposed to a low concentration of ozone. Am Rev Respir Dis. 1976 Jun;113(6):809–821. doi: 10.1164/arrd.1976.113.6.809. [DOI] [PubMed] [Google Scholar]
  42. Sevanian A., Elsayed N., Hacker A. D. Effects of vitamin E deficiency and nitrogen dioxide exposure on lung lipid peroxidation: use of lipid epoxides and malonaldehyde as measures of peroxidation. J Toxicol Environ Health. 1982 Oct-Nov;10(4-5):743–756. doi: 10.1080/15287398209530292. [DOI] [PubMed] [Google Scholar]
  43. Snyder A., Skoza L., Kikkawa Y. Comparative removal of ascorbic acid and other airway substances by sequential bronchoalveolar lavages. Lung. 1983;161(2):111–121. doi: 10.1007/BF02713849. [DOI] [PubMed] [Google Scholar]
  44. Steiner M., Anastasi J. Vitamin E. An inhibitor of the platelet release reaction. J Clin Invest. 1976 Mar;57(3):732–737. doi: 10.1172/JCI108331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Stump D. D., Roth E. F., Jr, Gilbert H. S. Simultaneous determination by high-performance liquid chromatography of tocopherol isomers, alpha-tocopheryl quinone, and cholesterol in red blood cells and plasma. J Chromatogr. 1984 Mar 9;306:371–376. doi: 10.1016/s0378-4347(00)80901-9. [DOI] [PubMed] [Google Scholar]
  46. Thomas H. V., Mueller P. K., Lyman R. L. Lipoperoxidation of lung lipids in rats exposed to nitrogen dioxide. Science. 1968 Feb 2;159(3814):532–534. doi: 10.1126/science.159.3814.532. [DOI] [PubMed] [Google Scholar]
  47. Vatassery G. T., Krezowski A. M., Eckfeldt J. H. Vitamin E concentrations in human blood plasma and platelets. Am J Clin Nutr. 1983 Jun;37(6):1020–1024. doi: 10.1093/ajcn/37.6.1020. [DOI] [PubMed] [Google Scholar]
  48. Ward J. A., Roberts R. J. Vitamin E inhibition of the effects of hyperoxia on the pulmonary surfactant system of the newborn rabbit. Pediatr Res. 1984 Apr;18(4):329–334. doi: 10.1203/00006450-198404000-00005. [DOI] [PubMed] [Google Scholar]
  49. Ward P. A., Till G. O., Kunkel R., Beauchamp C. Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury. J Clin Invest. 1983 Sep;72(3):789–801. doi: 10.1172/JCI111050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Willis R. J., Kratzing C. C. Ascorbic acid in rat lung. Biochem Biophys Res Commun. 1974 Aug 19;59(4):1250–1252. doi: 10.1016/0006-291x(74)90448-3. [DOI] [PubMed] [Google Scholar]

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