L-arginine transport is increased in macrophages generating nitric oxide.
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.
Bogle
R G
RG
Vascular Biology Research Centre, Biomedical Sciences Division, King's College, London, U.K.
Baydoun
A R
AR
Pearson
J D
JD
Moncada
S
S
Mann
G E
GE
D000818:Animals; D001120:Arginine / Q000493:pharmacokinetics*; D001692:Biological Transport; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D011994:Recombinant Proteins
D008070:Lipopolysaccharides; D009573:Nitrites; D011994:Recombinant Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine