Concomitant down-regulation of L-arginine transport and nitric oxide (NO) synthesis in rat alveolar macrophages by the polyamine spermine.
Polyamines can inhibit NO synthesis in activated macrophages (Mphi). Since NO synthesis in Mphi depends on cellular uptake of L-arginine, effects of polyamines on L-arginine uptake were studied. Rat alveolar Mphi (AMphi) were cultured in absence or presence of lipopolysaccharides (LPS) and/or different polyamines for up to 20 h. LPS increased nitrite accumulation about 10-fold and [(3)H]-L-arginine uptake about 2.5-fold, effects almost abolished by spermidine. Spermine had much weaker and putrescine no effects. The effects of spermine depended largely on the presence of serum in the culture medium, suggesting that spermine aldehyde might be involved. Spermine suppressed the mRNA for inducible nitric oxide synthase (iNOS) and that for a specific cationic amino acid transporter (CAT), CAT-2B. In conclusion, in Mphi spermine concomitantly down-regulates NO synthesis and cellular L-arginine uptake by suppressing the expression of iNOS and CAT-2B. By inhibiting specific functions of activated Mphi the polyamine oxidase-polyamine system may play a role as immuno-suppressive modulator.
Mössner
J
J
Institute of Pharmacology and Toxicology, University of Bonn, Reuterstr. 2b, D-53113 Bonn, Germany. racke.kurt@uni-bonn.de
Hammermann
R
R
Racké
K
K
D000818:Animals; D001120:Arginine / Q000493:pharmacokinetics*; D001692:Biological Transport; D002412:Cations; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013096:Spermine / Q000494:pharmacology*
D002412:Cations; D008070:Lipopolysaccharides; D013096:Spermine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase