Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1971 Feb;50(2):401–410. doi: 10.1172/JCI106507

Glutathione-dependent peroxidative metabolism in the alveolar macrophage

Molly T Vogt 1,2, Catherine Thomas 1,2, Charles L Vassallo 1,2, R E Basford 1,2, J Bernard L Gee 1,2
PMCID: PMC291936  PMID: 4395562

Abstract

Phagocytosis by rabbit alveolar macrophages (AM) is accompanied by increases in O2 consumption, glucose oxidation, and H2O2 formation. Two aspects of the interrelations between these metabolic features of phagocytosis have been studied.

First, the following evidence indicates that glutathione, glutathione reductase, and peroxidase serve as a cytoplasmic shuttle between H2O2 and NADPH-dependent glucose oxidation: (a) AM contain 5.9 mμmoles of reduced glutathione per 106 cells and exhibit glutathione peroxidase and NADPH-specific glutathione reductase activity; (b) oxidized glutathione potentiates NADP stimulation of glucose oxidation; (c) an artificial H2O2-generating system stimulates glucose oxidation; (d) the cell penetrating thiol inhibitor, N-ethylmaleimide diminishes glucose oxidation. This effect largely depends on inhibition of the glutathione system rather than on inhibition of either H2O2 formation or enzymes directly subserving glucose oxidation.

Second, three potential H2O2-generating oxidases have been sought. No cyanide-insensitive NADH or NADPH oxidase activity could be detected. D-amino acid oxidase activity was 0.48 ±0.07 U/106 cells with D-alanine as substrate.

Full text

PDF
401

Selected References

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

  1. BECK W. S. The control of leukocyte glycolysis. J Biol Chem. 1958 May;232(1):251–270. [PubMed] [Google Scholar]
  2. BEUTLER E. The glutathione instability of drug-sensitive red cells; a new method for the in vitro detection of drug sensitivity. J Lab Clin Med. 1957 Jan;49(1):84–95. [PubMed] [Google Scholar]
  3. Baehner R. L., Gilman N., Karnovsky M. L. Respiration and glucose oxidation in human and guinea pig leukocytes: comparative studies. J Clin Invest. 1970 Apr;49(4):692–700. doi: 10.1172/JCI106281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bénard B., DeGroot L. J. The role of hydrogen peroxide and glutathione in glucose oxidation by the thyroid. Biochim Biophys Acta. 1969 Jun 17;184(1):48–53. doi: 10.1016/0304-4165(69)90097-x. [DOI] [PubMed] [Google Scholar]
  5. CAGAN R. H., KARNOVSKY M. L. ENZYMATIC BASIS OF THE RESPIRATORY STIMULATION DURING PHAGOCYTOSIS. Nature. 1964 Oct 17;204:255–257. doi: 10.1038/204255a0. [DOI] [PubMed] [Google Scholar]
  6. CAHILL G. F., Jr, HASTINGS A. B., ASHMORE J., ZOTTU S. Studies on carbohydrate metabolism in rat liver slices. X. Factors in the regulation of pathways of glucose metabolism. J Biol Chem. 1958 Jan;230(1):125–135. [PubMed] [Google Scholar]
  7. COHN Z. A., HIRSCH J. G. The isolation and properties of the specific cytoplasmic granules of rabbit polymorphonuclear leucocytes. J Exp Med. 1960 Dec 1;112:983–1004. doi: 10.1084/jem.112.6.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Christophersen B. O. Formation of monohydroxy-polyenic fatty acids from lipid peroxides by a glutathione peroxidase. Biochim Biophys Acta. 1968 Sep 2;164(1):35–46. doi: 10.1016/0005-2760(68)90068-4. [DOI] [PubMed] [Google Scholar]
  9. Cline M. J., Lehrer R. I. D-amino acid oxidase in leukocytes: a possible D-amino-acid-linked antimicrobial system. Proc Natl Acad Sci U S A. 1969 Mar;62(3):756–763. doi: 10.1073/pnas.62.3.756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DIXON M., KLEPPE K. D-AMINO ACID OXIDASE. I. DISSOCIATION AND RECOMBINATION OF THE HOLOENZYME. Biochim Biophys Acta. 1965 Mar 22;96:357–367. doi: 10.1016/0005-2787(65)90556-3. [DOI] [PubMed] [Google Scholar]
  11. Evans A. E., Kaplan N. O. Pyridine nucleotide transhydrogenase in normal human and leukemic leukocytes. J Clin Invest. 1966 Aug;45(8):1268–1272. doi: 10.1172/JCI105433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gee J. B., Vassallo C. L., Bell P., Kaskin J., Basford R. E., Field J. B. Catalase-dependent peroxidative metabolism in the alveolar macrophage during phagocytosis. J Clin Invest. 1970 Jun;49(6):1280–1287. doi: 10.1172/JCI106340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Green G. M. Pulmonary clearance of infectious agents. Annu Rev Med. 1968;19:315–336. doi: 10.1146/annurev.me.19.020168.001531. [DOI] [PubMed] [Google Scholar]
  14. Haugaard N. Cellular mechanisms of oxygen toxicity. Physiol Rev. 1968 Apr;48(2):311–373. doi: 10.1152/physrev.1968.48.2.311. [DOI] [PubMed] [Google Scholar]
  15. Hochstein P., Utley H. Hydrogen peroxide detoxication by glutathione peroxidase and catalase in rat liver homogenates. Mol Pharmacol. 1968 Nov;4(6):574–579. [PubMed] [Google Scholar]
  16. IYER G. Y., QUESTEL J. H. NADPH and NADH oxidation by guinea pig polymorphonuclear leucocytes. Can J Biochem Physiol. 1963 Feb;41:427–434. [PubMed] [Google Scholar]
  17. Jacob H. S., Jandl J. H. Effects of sulfhydryl inhibition on red blood cells. 3. Glutathione in the regulation of the hexose monophosphate pathway. J Biol Chem. 1966 Sep 25;241(18):4243–4250. [PubMed] [Google Scholar]
  18. KARNOVSKY M. L. Metabolic basis of phagocytic activity. Physiol Rev. 1962 Jan;42:143–168. doi: 10.1152/physrev.1962.42.1.143. [DOI] [PubMed] [Google Scholar]
  19. MARGOLIASH E., NOVOGRODSKY A. A study of the inhibition of catalase by 3-amino-1:2:4:-triazole. Biochem J. 1958 Mar;68(3):468–475. doi: 10.1042/bj0680468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Menzel D. B. Toxicity of ozone, oxygen, and radiation. Annu Rev Pharmacol. 1970;10:379–394. doi: 10.1146/annurev.pa.10.040170.002115. [DOI] [PubMed] [Google Scholar]
  21. O'Brien P. J., Little C. Intracellular mechanisms for the decomposition of a lipid peroxide. II. Decomposition of a lipid peroxide by subcellular fractions. Can J Biochem. 1969 May;47(5):493–499. doi: 10.1139/o69-077. [DOI] [PubMed] [Google Scholar]
  22. OREN R., FARNHAM A. E., SAITO K., MILOFSKY E., KARNOVSKY M. L. Metabolic patterns in three types of phagocytizing cells. J Cell Biol. 1963 Jun;17:487–501. doi: 10.1083/jcb.17.3.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ouchi E., Selvaraj R. J., Sbarra A. J. The biochemical activities of rabbit alveolar macrophages during phagocytosis. Exp Cell Res. 1965 Dec;40(3):456–468. doi: 10.1016/0014-4827(65)90226-0. [DOI] [PubMed] [Google Scholar]
  24. Paglia D. E., Valentine W. N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967 Jul;70(1):158–169. [PubMed] [Google Scholar]
  25. Paul B. B., Strauss R. R., Jacobs A. A., Sbarra A. J. Function of h(2)o(2), myeloperoxidase, and hexose monophosphate shunt enzymes in phagocytizing cells from different species. Infect Immun. 1970 Apr;1(4):338–344. doi: 10.1128/iai.1.4.338-344.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Reed P. W. Glutathione and the hexose monophosphate shunt in phagocytizing and hydrogen peroxide-treated rat leukocytes. J Biol Chem. 1969 May 10;244(9):2459–2464. [PubMed] [Google Scholar]
  27. SBARRA A. J., KARNOVSKY M. L. The biochemical basis of phagocytosis. I. Metabolic changes during the ingestion of particles by polymorphonuclear leukocytes. J Biol Chem. 1959 Jun;234(6):1355–1362. [PubMed] [Google Scholar]
  28. Srivastava S. K., Beutler E. The transport of oxidized glutathione from human erythrocytes. J Biol Chem. 1969 Jan 10;244(1):9–16. [PubMed] [Google Scholar]
  29. Strauss R. R., Paul B. B., Jacobs A. A., Sbarra A. J. The role of the phagocyte in host-parasite interactions. XIX. Leukocytic glutathione reductase and its involvement in phagocytosis. Arch Biochem Biophys. 1969 Dec;135(1):265–271. doi: 10.1016/0003-9861(69)90539-6. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Wills E. D., Wilkinson A. E. Release of enzymes from lysosomes by irradiation and the relation of lipid peroxide formation to enzyme release. Biochem J. 1966 Jun;99(3):657–666. doi: 10.1042/bj0990657. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES