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Journal of Allergy
Volume 2011 (2011), Article ID 736319, 12 pages
http://dx.doi.org/10.1155/2011/736319
Review Article

Arginase and Arginine Dysregulation in Asthma

1Bay Area Pediatric Pulmonary Medical Corporation, Children's Hospital & Research Center Oakland, Oakland, CA 94609, USA
2Department of Emergency Medicine, Children's Hospital & Research Center Oakland, Oakland, CA 94609, USA

Received 1 December 2010; Revised 7 February 2011; Accepted 10 February 2011

Academic Editor: Stephen P. Peters

Copyright © 2011 Renée C. Benson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In recent years, evidence has accumulated indicating that the enzyme arginase, which converts L-arginine into L-ornithine and urea, plays a key role in the pathogenesis of pulmonary disorders such as asthma through dysregulation of L-arginine metabolism and modulation of nitric oxide (NO) homeostasis. Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Through substrate competition, arginase decreases bioavailability of L-arginine for nitric oxide synthase (NOS), thereby limiting NO production with subsequent effects on airway tone and inflammation. By decreasing L-arginine bioavailability, arginase may also contribute to the uncoupling of NOS and the formation of the proinflammatory oxidant peroxynitrite in the airways. Finally, arginase may play a role in the development of chronic airway remodeling through formation of L-ornithine with downstream production of polyamines and L-proline, which are involved in processes of cellular proliferation and collagen deposition. Further research on modulation of arginase activity and L-arginine bioavailability may reveal promising novel therapeutic strategies for asthma.