HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/2/L313    most recent 00434.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Endo, M. Articles by Gotoh, T. Search for Related Content PubMed PubMed Citation Articles by Endo, M. Articles by Gotoh, T.

Induction of arginase I and II in bleomycin-induced fibrosis of mouse lung

¹Department of Molecular Genetics, ²First Department of Internal Medicine, and ³Second Department of Pathology, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan

Submitted 17 December 2002 ; accepted in final form 31 March 2003

Arginase, which hydrolyzes arginine to urea and ornithine, is a precursor for the synthesis of polyamines and proline, which is abundant in collagen. The supply of proline can be a crucial factor in the process of lung fibrosis. We investigated the induction of arginine metabolic enzymes in bleomycin-induced mouse lung fibrosis. Histological studies and quantification of lung hydroxyproline showed that lung fibrosis develops in up to 14 days after bleomycin treatment. Under these conditions, collagen I mRNA was induced gradually in up to 15 days, and the content of hydroxyproline reached a maximum at 10 days. Arginase I mRNA was undetectable before bleomycin treatment but was induced 5–10 days after this treatment. Arginase I protein was induced at 7 days and remained little changed for up to 10 days and decreased at 14 days. On the other hand, arginase II mRNA that was detectable before treatment was increased gradually for up to 10 days and decreased at 14 days. Arginase II protein began to increase at day 5, increased for up to 10 days, and was decreased at day 14. mRNAs for cationic amino acid transporter-2 and ornithine decarboxylase were induced in a manner similar to that seen with collagen I mRNA. Immunohistochemical analysis showed that arginase I is induced in macrophages, whereas arginase II is induced in various cell types, including macrophages and myofibroblasts, and roughly colocalizes with the collagen-specific chaperone heat shock protein 47. Our findings suggest that arginine metabolic enzymes play an important role in the development of lung fibrosis, at least in mice.

macrophage; lung fibrosis; arginine; collagen

This article has been cited by other articles:

				B. Gangadharan, M. A. Hoeve, J. E. Allen, B. Ebrahimi, S. M. Rhind, B. M. Dutia, and A. A. Nash Murine gammaherpesvirus-induced fibrosis is associated with the development of alternatively activated macrophages J. Leukoc. Biol., July 1, 2008; 84(1): 50 - 58. [Abstract] [Full Text] [PDF]

				J.-M. Tadie, P. Henno, I. Leroy, C. Danel, E. Naline, C. Faisy, M. Riquet, M. Levy, D. Israel-Biet, and C. Delclaux Role of nitric oxide synthase/arginase balance in bronchial reactivity in patients with chronic obstructive pulmonary disease Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L489 - L497. [Abstract] [Full Text] [PDF]

				K. Kitowska, D. Zakrzewicz, M. Konigshoff, I. Chrobak, F. Grimminger, W. Seeger, P. Bulau, and O. Eickelberg Functional role and species-specific contribution of arginases in pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L34 - L45. [Abstract] [Full Text] [PDF]

				A. L. Mora, E. Torres-Gonzalez, M. Rojas, C. Corredor, J. Ritzenthaler, J. Xu, J. Roman, K. Brigham, and A. Stecenko Activation of Alveolar Macrophages via the Alternative Pathway in Herpesvirus-Induced Lung Fibrosis Am. J. Respir. Cell Mol. Biol., October 1, 2006; 35(4): 466 - 473. [Abstract] [Full Text] [PDF]

				A. Erdely, D. Kepka-Lenhart, M. Clark, P. Zeidler-Erdely, M. Poljakovic, W. J. Calhoun, and S. M. Morris Jr Inhibition of phosphodiesterase 4 amplifies cytokine-dependent induction of arginase in macrophages Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L534 - L539. [Abstract] [Full Text] [PDF]

				P. Misson, S. van den Brule, V. Barbarin, D. Lison, and F. Huaux Markers of macrophage differentiation in experimental silicosis J. Leukoc. Biol., November 1, 2004; 76(5): 926 - 932. [Abstract] [Full Text] [PDF]