Effects of excessive single among acids on arginine transport and nitrite production by avian macrophages

L-arginine was transported by a saturable cationic amlno add transporter with Km of 1.1, 1.3, 0.95 and 0.95 mM and Vmax of 0.6, 1.2, 0.19, 0.25 untol/hr/10⁶ cells, respectively, in unsUmulatedHDll cells, stimulated (LPS-treated) HD11 cells, unstimulated chicken peritoneal macrophages and stimulated chicken peritoneal macrophages. The Kl for the inhibition of L-arginine transport by both L-lysine and L-omithine in stimulated HD11 cells was 0.08 mM. When the arginine concentration in incubation media was 0.1 mM each of the L-branched amino acids (L-BCAA) at 10 mM concentration inhibited the uptake of L-arginine to a similar extent (about 60%). L-pbenylalanine caused about 30% inhibition of L-arginine uptake. L-hlstldlne had a greater Inhibitory effect than L-BCAA and L-phenylalanine. L-lysine, L-omithine and L-histidine suppressed nitrite production in a concentration-dependent manner when cells were cultured in media containing 0.1 mM L-arginine. L-BCAA did not affect nitrite production in HD11 cells even at high concentrations. L-phenylalanine did not inhibit nitrite production at lower concentrations, but caused significant suppression at a high concentration (ca. 10 mM). The competitive utilization of tetrahydrobiopterin, a cofactor for nitric oxide synthase and phenylalanine hydroxylase, may contribute to the inhibition of nitrite formation in HD11 cells by L-phenylalanlne. Effects of cationic amino adds on Larginine transport and nitrite formation were also observed in chicken peritoneal macrophages. L-lystae and L-omtthine Inhibited the uptake of L-arginine with a Ki of 0.01 mM In stimulated peritoneal macrophages. The neutral amino adds, L-phenylalanine and L-dtniUine, and the anionic amino add, L-aspartate in contrast, tended to increase nitrite production in peritoneal macrophages. The results indicate that high concentrations of extracellular L-lysine, L-ornithine, L-phenylalanine and L-histidine may compromise immunity in the chicken.