help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hammermann, R.
Right arrow Articles by Racké, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hammermann, R.
Right arrow Articles by Racké, K.

Am. J. Respir. Cell Mol. Biol., Volume 21, Number 2, August, 1999 155-162

Cationic Proteins Inhibit L-Arginine Uptake in Rat Alveolar Macrophages and Tracheal Epithelial Cells
Implications for Nitric Oxide Synthesis

Rainer Hammermann, Joachim Hirschmann, Claudia Hey, Jutta Mössner, Gert Folkerts, Frans P. Nijkamp, Ignaz Wessler, and Kurt Racké

Institute of Pharmacology and Toxicology, University of Bonn, Bonn; Department of Pharmacology, University of Mainz, Mainz, Germany; and Faculty of Pharmacy, University of Utrecht, Utrecht, The Netherlands

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 [3H]-L-arginine, nitrite accumulation, and the turnover of [3H]-L-arginine by nitric oxide (NO) synthase and arginase (formation of [3H]-L-citrulline and [3H]-L-ornithine, respectively) were studied. Poly-L-arginine reduced [3H]-L-arginine uptake in rat AMPhi and tracheal epithelial cells in a concentration-dependent manner (at 300 µg/ml by 70%). Poly-L-lysine, protamine, and major basic protein (each up to 300 µg/ml) tested in rat AMPhi inhibited [3H]-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 µg/ml), accumulated 1.4 and 3.5 nmol/106 cells nitrite, respectively. Addition of 100 µM 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 µg/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 µg/ml) inhibited [3H]-L-citrulline formation by AMPhi stronger than that of [3H]-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.




This article has been cited by other articles:


Home page
 Eur Respir JHome page
H. Meurs, R. Gosens, and J. Zaagsma
Airway hyperresponsiveness in asthma: lessons from in vitro model systems and animal models
Eur. Respir. J., August 1, 2008; 32(2): 487 - 502.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Yeramian, L. Martin, N. Serrat, L. Arpa, C. Soler, J. Bertran, C. McLeod, M. Palacin, M. Modolell, J. Lloberas, et al.
Arginine Transport via Cationic Amino Acid Transporter 2 Plays a Critical Regulatory Role in Classical or Alternative Activation of Macrophages
J. Immunol., May 15, 2006; 176(10): 5918 - 5924.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
N. E. King, M. E. Rothenberg, and N. Zimmermann
Arginine in Asthma and Lung Inflammation
J. Nutr., October 1, 2004; 134(10): 2830S - 2836S.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Endo, S. Oyadomari, Y. Terasaki, M. Takeya, M. Suga, M. Mori, and T. Gotoh
Induction of arginase I and II in bleomycin-induced fibrosis of mouse lung
Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L313 - L321.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
R. Hammermann, M. D. M. Dreißig, J. Mössner, M. Fuhrmann, L. Berrino, M. Göthert, and K. Racké
Nuclear Factor-kappa B Mediates Simultaneous Induction of Inducible Nitric-Oxide Synthase and Up-Regulation of the Cationic Amino Acid Transporter CAT-2B in Rat Alveolar Macrophages
Mol. Pharmacol., April 13, 2001; 58(6): 1294 - 1302.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
F. H. Guo, S. A. A. Comhair, S. Zheng, R. A. Dweik, N. T. Eissa, M. J. Thomassen, W. Calhoun, and S. C. Erzurum
Molecular Mechanisms of Increased Nitric Oxide (NO) in Asthma: Evidence for Transcriptional and Post-Translational Regulation of NO Synthesis
J. Immunol., June 1, 2000; 164(11): 5970 - 5980.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. Mark Madison and C. M. Schramm
Cationic Proteins and Bronchial Hyperresponsiveness
Am. J. Respir. Cell Mol. Biol., May 1, 2000; 22(5): 513 - 516.
[Full Text]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. P. Sanders
Nitric Oxide in Asthma . Pathogenic, Therapeutic, or Diagnostic?
Am. J. Respir. Cell Mol. Biol., August 1, 1999; 21(2): 147 - 149.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 1999 American Thoracic Society. 		  ATS Best of the Web