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. 1992 May 15;284(Pt 1):15–18. doi: 10.1042/bj2840015

L-arginine transport is increased in macrophages generating nitric oxide.

R G Bogle 1, A R Baydoun 1, J D Pearson 1, S Moncada 1, G E Mann 1
PMCID: PMC1132690  PMID: 1599394

Abstract

Transport of L-arginine and nitrite production were examined in the murine macrophage cell line J774. Bacterial lipopolysaccharide (LPS) induced a dose- and time-dependent stimulation of nitrite production, which was further increased in the presence of interferon-gamma. Nitrite synthesis was absolutely dependent on extracellular L-arginine and inhibited in the presence of L-lysine or L-ornithine. In unactivated J774 cells L-arginine transport was saturable, with an apparent Km of 0.14 +/- 0.04 mM and Vmax. of 15 +/- 2 nmol/h per 10(6) cells. LPS (1 microgram/ml) induced a time-dependent stimulation of L-arginine transport, and after 24 h the Vmax. increased to 34 +/- 2 nmol/h per 10(6) cells. These findings indicate that activation of J774 cells with LPS produces an increase in both L-arginine transport and nitrite synthesis. The elevated rate of L-arginine transport in activated J774 cells may provide a mechanism for sustained substrate supply during enhanced utilization of L-arginine for the generation of NO.

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Selected References

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

  1. Adams D. O., Hamilton T. A. The cell biology of macrophage activation. Annu Rev Immunol. 1984;2:283–318. doi: 10.1146/annurev.iy.02.040184.001435. [DOI] [PubMed] [Google Scholar]
  2. Albina J. E., Caldwell M. D., Henry W. L., Jr, Mills C. D. Regulation of macrophage functions by L-arginine. J Exp Med. 1989 Mar 1;169(3):1021–1029. doi: 10.1084/jem.169.3.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Albina J. E., Mills C. D., Barbul A., Thirkill C. E., Henry W. L., Jr, Mastrofrancesco B., Caldwell M. D. Arginine metabolism in wounds. Am J Physiol. 1988 Apr;254(4 Pt 1):E459–E467. doi: 10.1152/ajpendo.1988.254.4.E459. [DOI] [PubMed] [Google Scholar]
  4. Bannai S., Sato H., Ishii T., Taketani S. Enhancement of glutathione levels in mouse peritoneal macrophages by sodium arsenite, cadmium chloride and glucose/glucose oxidase. Biochim Biophys Acta. 1991 Apr 17;1092(2):175–179. doi: 10.1016/0167-4889(91)90153-o. [DOI] [PubMed] [Google Scholar]
  5. Bonventre P. F., Straus D., Baughn R. E., Imhoff J. Enhancement of carrier-mediated transport after immunologic activation of peritoneal macrophages. J Immunol. 1977 May;118(5):1827–1835. [PubMed] [Google Scholar]
  6. Currie G. A. Activated macrophages kill tumour cells by releasing arginase. Nature. 1978 Jun 29;273(5665):758–759. doi: 10.1038/273758a0. [DOI] [PubMed] [Google Scholar]
  7. Currie G. A., Gyure L., Cifuentes L. Microenvironmental arginine depletion by macrophages in vivo. Br J Cancer. 1979 Jun;39(6):613–620. doi: 10.1038/bjc.1979.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Di Rosa M., Radomski M., Carnuccio R., Moncada S. Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1246–1252. doi: 10.1016/0006-291x(90)91583-e. [DOI] [PubMed] [Google Scholar]
  9. Granger D. L., Hibbs J. B., Jr, Perfect J. R., Durack D. T. Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages. J Clin Invest. 1990 Jan;85(1):264–273. doi: 10.1172/JCI114422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Guidotti G. G., Gazzola G. C., Borghetti A. F., Franchi-Gazzola R. Adaptive regulation of amino acid transport across the cell membrane in avian and mammalian tissues. Biochim Biophys Acta. 1975 Oct 6;406(2):264–279. doi: 10.1016/0005-2736(75)90009-7. [DOI] [PubMed] [Google Scholar]
  11. Hauschildt S., Lückhoff A., Mülsch A., Kohler J., Bessler W., Busse R. Induction and activity of NO synthase in bone-marrow-derived macrophages are independent of Ca2+. Biochem J. 1990 Sep 1;270(2):351–356. doi: 10.1042/bj2700351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hevel J. M., White K. A., Marletta M. A. Purification of the inducible murine macrophage nitric oxide synthase. Identification as a flavoprotein. J Biol Chem. 1991 Dec 5;266(34):22789–22791. [PubMed] [Google Scholar]
  13. Hibbs J. B., Jr, Taintor R. R., Vavrin Z., Rachlin E. M. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988 Nov 30;157(1):87–94. doi: 10.1016/s0006-291x(88)80015-9. [DOI] [PubMed] [Google Scholar]
  14. Hibbs J. B., Jr, Vavrin Z., Taintor R. R. L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J Immunol. 1987 Jan 15;138(2):550–565. [PubMed] [Google Scholar]
  15. Jorens P. G., Van Overveld F. J., Bult H., Vermeire P. A., Herman A. G. L-arginine-dependent production of nitrogen oxides by rat pulmonary macrophages. Eur J Pharmacol. 1991 Aug 6;200(2-3):205–209. doi: 10.1016/0014-2999(91)90573-9. [DOI] [PubMed] [Google Scholar]
  16. Keller R., Geiges M., Keist R. L-arginine-dependent reactive nitrogen intermediates as mediators of tumor cell killing by activated macrophages. Cancer Res. 1990 Mar 1;50(5):1421–1425. [PubMed] [Google Scholar]
  17. Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
  18. Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Orlowski M., Meister A. The gamma-glutamyl cycle: a possible transport system for amino acids. Proc Natl Acad Sci U S A. 1970 Nov;67(3):1248–1255. doi: 10.1073/pnas.67.3.1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pofit J. F., Strauss P. R. Membrane transport by macrophages in suspension and adherent to glass. J Cell Physiol. 1977 Aug;92(2):249–255. doi: 10.1002/jcp.1040920213. [DOI] [PubMed] [Google Scholar]
  21. Rouzer C. A., Scott W. A., Griffith O. W., Hamill A. L., Cohn Z. A. Glutathione metabolism in resting and phagocytizing peritoneal macrophages. J Biol Chem. 1982 Feb 25;257(4):2002–2008. [PubMed] [Google Scholar]
  22. Sato H., Ishii T., Sugita Y., Bannai S. Changes in neutral amino acid transport activity in myeloid leukemia cells differentiated by lipopolysaccharide. Biochim Biophys Acta. 1989 Aug 7;983(2):259–263. doi: 10.1016/0005-2736(89)90242-3. [DOI] [PubMed] [Google Scholar]
  23. Sato H., Ishii T., Sugita Y., Bannai S. Induction of cationic amino acid transport activity in mouse peritoneal macrophages by lipopolysaccharide. Biochim Biophys Acta. 1991 Oct 14;1069(1):46–52. doi: 10.1016/0005-2736(91)90102-e. [DOI] [PubMed] [Google Scholar]
  24. Strauss P. R., Berlin R. D. Effects of serum on membrane transport. I. Separation and preliminary characterization of factors which depress lysine or stimulate adenosine transport in rabbit alveolar macrophages. J Exp Med. 1973 Feb 1;137(2):359–368. doi: 10.1084/jem.137.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stuehr D. J., Marletta M. A. Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7738–7742. doi: 10.1073/pnas.82.22.7738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stuehr D. J., Marletta M. A. Synthesis of nitrite and nitrate in murine macrophage cell lines. Cancer Res. 1987 Nov 1;47(21):5590–5594. [PubMed] [Google Scholar]
  27. Stuehr D. J., Nathan C. F. Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med. 1989 May 1;169(5):1543–1555. doi: 10.1084/jem.169.5.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tsan M. F., Berlin R. D. Membrane transport in the rabbit alveolar macrophage. The specificity and characteristics of amino acid transport systems. Biochim Biophys Acta. 1971 Jul 6;241(1):155–169. doi: 10.1016/0005-2736(71)90313-0. [DOI] [PubMed] [Google Scholar]
  29. Watanabe H., Bannai S. Induction of cystine transport activity in mouse peritoneal macrophages. J Exp Med. 1987 Mar 1;165(3):628–640. doi: 10.1084/jem.165.3.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. White M. F. The transport of cationic amino acids across the plasma membrane of mammalian cells. Biochim Biophys Acta. 1985 Dec 9;822(3-4):355–374. doi: 10.1016/0304-4157(85)90015-2. [DOI] [PubMed] [Google Scholar]
  31. Yui Y., Hattori R., Kosuga K., Eizawa H., Hiki K., Kawai C. Purification of nitric oxide synthase from rat macrophages. J Biol Chem. 1991 Jul 5;266(19):12544–12547. [PubMed] [Google Scholar]

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