Hammermann_1999_Am.J.Respir.Cell.Mol.Biol_21_155

Reference

Title : Cationic proteins inhibit L-arginine uptake in rat alveolar macrophages and tracheal epithelial cells. Implications for nitric oxide synthesis - Hammermann_1999_Am.J.Respir.Cell.Mol.Biol_21_155
Author(s) : Hammermann R , Hirschmann J , Hey C , Mossner J , Folkerts G , Nijkamp FP , Wessler I , Racke K
Ref : American Journal of Respiratory Cellular & Molecular Biology , 21 :155 , 1999
Abstract :

Eosinophil-derived cationic proteins play an essential role in the pathogenesis of bronchial asthma. We tested whether cationic proteins interfere with the cationic amino-acid transport in alveolar macrophages (AMPhi) and tracheal epithelial cells, and whether L-arginine-dependent pathways were affected. The effect of cationic polypeptides on cellular uptake of [(3)H]-L-arginine, nitrite accumulation, and the turnover of [(3)H]-L-arginine by nitric oxide (NO) synthase and arginase (formation of [(3)H]-L-citrulline and [(3)H]-L-ornithine, respectively) were studied. Poly-L-arginine reduced [(3)H]-L-arginine uptake in rat AMPhi and tracheal epithelial cells in a concentration-dependent manner (at 300 microgram/ml by 70%). Poly-L-lysine, protamine, and major basic protein (each up to 300 microgram/ml) tested in rat AMPhi inhibited [(3)H]-L-arginine uptake by 35 to 50%. During 6 h incubation in amino acid-free Krebs solution, rat AMPhi, precultured in the absence or presence of LPS (1 microgram/ml), accumulated 1.4 and 3.5 nmol/10(6) cells nitrite, respectively. Addition of 100 microM L-arginine increased nitrite accumulation by 70 and 400% in control and lipopolysaccharide-treated AMPhi, respectively. Nitrite accumulation in the presence of L-arginine was reduced by poly-L-arginine and poly-L-lysine (100 and 300 microgram/ml) by 60 to 85% and 20 to 30%, respectively. Poly-L-arginine, but not poly-L-lysine, inhibited nitrite accumulation already in the absence of extracellular L-arginine. Poly-L-arginine (300 microgram/ml) inhibited [(3)H]-L-citrulline formation by AMPhi stronger than that of [(3)H]-L-ornithine. We conclude that cationic proteins can inhibit cellular transport of L-arginine and this can limit NO synthesis. Poly-L-arginine inhibits L-arginine uptake more effectively than other cationic proteins and exerts additional direct inhibitory effects on NO synthesis.

PubMedSearch : Hammermann_1999_Am.J.Respir.Cell.Mol.Biol_21_155
PubMedID: 10423396

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Citations formats

Hammermann R, Hirschmann J, Hey C, Mossner J, Folkerts G, Nijkamp FP, Wessler I, Racke K (1999)
Cationic proteins inhibit L-arginine uptake in rat alveolar macrophages and tracheal epithelial cells. Implications for nitric oxide synthesis
American Journal of Respiratory Cellular & Molecular Biology 21 :155

Hammermann R, Hirschmann J, Hey C, Mossner J, Folkerts G, Nijkamp FP, Wessler I, Racke K (1999)
American Journal of Respiratory Cellular & Molecular Biology 21 :155