Abstract
Transport ofl-arginine and nitrite production were examined in the murine macrophage cell line J774. Lipopolysaccharide (LPS) induced a dose- and time-dependent stimulation of nitrite production which was further increased in the presence of interferon-γ (INF-γ). Nitrite synthesis was dependent on extracellular arginine and inhibited in the presence ofl-lysine. Treatment of cells with LPS and IFN-γ caused a reduction in intracellularl-arginine concentration which was accompanied by increases in the levels ofl-citrulline in both the cells and culture medium.
These findings indicate that activation of J774 cells with LPS produces an increase in bothl-arginine transport and nitrite synthesis. The elevated rate ofl-arginine transport in activated J774 cells may provide a mechanism for sustained substrate supply during enhanced utilization ofl-arginine for the generation of nitric oxide.
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J. B. Hibbs, R. R. Taintor, Z. Vavrin and E. M. Rachlin,Nitric oxide: A cytotoxic activated macrophage effector molecule. Biochem. Biophys. Res. Commun.157, 87–94 (1988).
D. J. Stuehr and C. F. Nathan,Nitric oxide: A macrophage product responsible for cytostasis and respiratory inhibition in tumour target cells. J. Exp. Med.169, 1543–1555 (1989).
M. Di-Rosa, M. Radomski, R. Carnuccio and S. Moncada,Glucocorticoids inhibition the induction of NO synthase in culture murine macrophages. Biochem. Biophys. Res. Commun.172, 1246–1252 (1990).
J. E. Albina, C. D. Mills, W. L. Henry, B. Caldwell and M. D. Caldwell,Regulation of macrophage physiology by l -arginine: Role of oxidative deiminase pathway. J. Immunol.254, E479-E467 (1989).
J. E. Albina, M. D. Caldwell, W. L. Henry and C. D. Mills,Regulation of macrophage functions by l -arginine. J. Exp. Med.169, 1021–1029 (1989).
A. R. Baydoun, P. Emery, J. D. Pearson and G. E. Mann,Substrate dependent regulation of amino acid concentrations in cultured bovine aortic endothelial cells. Biochem. Biophys. Res. Commun.173, 940–948 (1990).
R. G. Bogle, A. R. Baydoun, S. Moncada, J. D. Pearson and G. E. Mann,Transport of l -arginine is increased in macrophages generating nitric oxide. Biochem. J.284, 15–18 (1992).
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Baydoun, A.R., Bogle, R.G., Pearson, J.D. et al. Arginine uptake and metabolism in cultured murine macrophages. Agents and Actions 38 (Suppl 2), C127–C129 (1993). https://doi.org/10.1007/BF01991160
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DOI: https://doi.org/10.1007/BF01991160